Cancer Research and Treatment

Original Articles

Early On-Treatment Host Fitness Dynamics Refine Prognostic Stratification in Advanced NSCLC Receiving First-Line Immunotherapy: Se-Il Go, Jinyong Kim, Sehhoon Park, Il Hwan Kim, Dong-Wan Kim, Yun-Gyoo Lee, Jang Ho Cho, Eun Kyung Cho, Hyun Woo Lee, Ji-Hyun Park, Eun Joo Kang, Youngjoo Lee, Nak-Hoon Son, So Hyeon Gwon, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Gyeong-Won Lee; Received June 7, 2026 Accepted August 7, 2026 Published online August 10, 2026; DOI: https://doi.org/10.4143/crt.2026.0607 [Accepted]

Abstract PDF: Purpose
We assessed whether baseline and early on-treatment measurements of host fitness using the Prognostic Nutritional Index (PNI) provide complementary prognostic information in advanced non-small cell lung cancer (NSCLC).
Materials and Methods
Within the prospective, multicenter OPTIMUS trial, 497 patients with advanced NSCLC receiving first-line pembrolizumab-based therapy were analyzed. PNI was calculated from serum albumin and lymphocyte count at baseline and before cycle 2 (early on-treatment). Using a cutoff of 50.5, 441 patients with paired measurements were classified by baseline/early on-treatment PNI status as high/high, high/low, low/high, or low/low.
Results
Low baseline PNI was associated with lower objective response and higher treatment-related mortality. Among responders, low early on-treatment PNI was associated with lower odds of 6-month response maintenance (adjusted OR, 0.40; 95% CI, 0.17–0.97). Response-maintenance rates were lowest in the low/low group at both 6 and 12 months. In multivariable analyses including both PNI time points, low early on-treatment PNI was associated with shorter PFS (HR, 1.50; 95% CI, 1.11–2.04), whereas low baseline PNI was not (HR, 1.27; 95% CI, 0.94–1.71). Both low baseline PNI (HR, 1.53; 95% CI, 1.07–2.19) and low early on-treatment PNI (HR, 1.47; 95% CI, 1.02–2.12) were associated with shorter OS. The higher mortality risk in the low/low group was generally consistent across PD-L1 expression and treatment regimen subgroups.
Conclusion
PNI assessment at baseline and before cycle 2 provides complementary prognostic information, with early on-treatment PNI particularly related to PFS and response durability (ClinicalTrials.gov Identifier: NCT04909164).

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Neutrophil-to-Lymphocyte Ratio and Extrahepatic Spread Predict Response and Survival in Unresectable Hepatocellular Carcinoma: Dong Yun Kim, Heechul Nam, Jun Yong Park, Sang Hoon Ahn, Sung Won Lee, Do Young Kim; Received May 8, 2026 Accepted July 3, 2026 Published online July 7, 2026; DOI: https://doi.org/10.4143/crt.2026.0498 [Accepted]

Abstract PDF: Purpose
Identifying nonresponders to atezolizumab plus bevacizumab (AB) remains challenging in unresectable hepatocellular carcinoma (uHCC). We aimed to develop and externally validate a simple risk scoring system using baseline neutrophil-to-lymphocyte ratio (NLR) and extrahepatic spread (EHS) to predict treatment outcomes.
Materials and Methods
We included 304 patients with uHCC receiving first-line AB from multiple Korean centers (discovery, n = 220; validation, n = 84). Study outcomes included objective response rate (ORR) assessed by modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), and progression-free survival (PFS). Multivariable analysis identified high NLR (>4.575) and EHS as independent predictors of nonresponse. The NLR-EHS score assigned 2 points for high NLR and 1 point for EHS (range, 0–3).
Results
In the discovery cohort, the score predicted nonresponse with an area under the receiver operating characteristic curve (AUC) of 0.749 (95% CI, 0.688–0.810); ORR fell across low- (0), moderate- (1–2), and high-risk (3) groups (67.3%, 47.7%, and 8.2%; p < 0.001). Validation confirmed comparable discrimination (AUC, 0.705; 95% CI, 0.603–0.806) and a consistent ORR gradient (77.8%, 54.2%, and 22.2%; p < 0.001). The score was prognostic for OS in discovery (HR, 1.28; p = 0.003) and validation cohorts (HR, 1.45; p = 0.007), remaining significant after adjustment (adjusted HR, 1.25 and 1.61, respectively). High-risk patients had inferior median OS (6.9 vs. 17.1 months in validation).
Conclusion
The NLR-EHS score is a practical tool for stratifying nonresponse risk and survival in uHCC patients receiving AB, facilitating early identification of high-risk patients who may benefit from alternative strategies.

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Biomarker Testing Practices for Non–Small Cell Lung Cancer: Survey Insights from South Korean Pathology Laboratories: Sehui Kim, Dajeong Kim, Lucia Kim, Wan-Seop Kim; Received September 29, 2025 Accepted January 28, 2026 Published online January 30, 2026; DOI: https://doi.org/10.4143/crt.2025.927 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Molecular biomarker testing is essential for lung cancer management and precision medicine. This study evaluated biomarker testing practices for non–small cell lung cancer (NSCLC) across pathology laboratories in South Korea.
Materials and Methods
A nationwide survey of 30 pathology laboratories assessed testing policies, biomarker adoption, testing platforms, next-generation sequencing (NGS) implementation, reporting practices, turnaround times (TATs), and perceived challenges.
Results
All institutions routinely performed biomarker testing; 20 (66.7%) employed reflex testing at least in part. Tissue was the primary specimen type, and cytology and liquid biopsy specimens were accepted by 90.0% and 46.7% of institutions, respectively. For non-squamous NSCLC, all institutions tested epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, and programmed cell death ligand 1 (PD-L1), with additional testing for BRAF (86.7%) and KRAS (80.0%); other actionable targets were rarely tested outside NGS. In squamous NSCLC, PD-L1 was routinely assessed, whereas other drivers were tested less frequently. All institutions performed tissue-based NGS using companion diagnostic (CDx) and/or non-CDx platforms, and liquid biopsy–based NGS was available in 46.7% of institutions. Median TATs were 2-3, 5, 9, 19, and 15 days for immunohistochemistry, polymerase chain reaction, fluorescence in situ hybridization, tissue-based NGS, and liquid biopsy–based NGS, respectively. Reported barriers included limited sample availability, workforce shortages, prolonged TATs, regulatory restrictions, and lack of standardization.
Conclusion
Biomarker testing is widely implemented in South Korea, with increasing integration of NGS. Despite alignment with international recommendations, systemic and policy reforms are needed to harmonize workflows, reduce variability, and optimize precision oncology.

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Association between FGFR2b Positivity and Survival Outcomes of Patients with Gastric Cancer Treated with First-Line Nivolumab Plus Chemotherapy: Hyung-Don Kim, Heonwoo Lee, Hyungeun Lee, Meesun Moon, Jaewon Hyung, Jungeun Ma, Young Soo Park, Min-Hee Ryu; Received June 6, 2025 Accepted November 22, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4143/crt.2025.598 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy.
Materials and Methods
This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1–9% as low expression.
Results
FGFR2b overexpression and positivity were identified in 9.3% and 16.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy.
Conclusion
FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.

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Patient-derived organoids in gastric cancer: bridging the tumor microenvironment to functional precision oncology
Ji Ma, Xinyang Liu, Hongtao Xu, Chuan Jiang
Frontiers in Bioengineering and Biotechnology.2026;[Epub] CrossRef

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Extracellular Vesicle-Derived Adenosine as a Diagnostic Metabolic Biomarker for Pancreatic Ductal Adenocarcinoma: Tao Xia, Wenhui Ouyang, Jie Wang, Jinjing Wang, Yiping Mou, Zhengquan Yang, Hezhi Fang, Shanying Gui; Received May 12, 2025 Accepted September 11, 2025 Published online September 24, 2025; DOI: https://doi.org/10.4143/crt.2025.510 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This study aimed to identify more accurate plasma biomarkers by profiling extracellular vesicles (EVs), which are enriched in tumorderived metabolites and proteins.
Materials and Methods
Plasma samples were collected under strict fasting and standardized processing protocols from patients diagnosed with PDAC, chronic pancreatitis, and tumor-free controls. EVs were isolated from these plasma samples and subjected to comprehensive metabolomic and proteomic profiling to identify disease-specific biomarkers.
Results
A biomarker panel comprising adenosine, adenine, and N-acetylneuraminate (AAN) demonstrated outstanding diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.968 (95% confidence interval [CI], 0.92 to 1.00). At a fixed specificity of 96.8%, the panel yielded a sensitivity of 95.0% (95% CI, 85.0% to 100.0%), significantly reducing the classification error from 30% with carbohydrate antigen 19-9 (CA19-9) to 5% with the AAN panel. Among individual markers, adenosine alone showed high diagnostic power (AUC, 0.952), correlating with increased expression of 5′-nucleotidase ecto (NT5E), indicative of elevated extracellular purine metabolism. Importantly, these features were unique to the EV compartment and outperformed markers derived from total plasma metabolite profiles.
Conclusion
The integration of EV metabolomics and proteomics revealed enhanced purine metabolism, particularly elevated extracellular adenosine, as a distinctive hallmark of PDAC. EV-derived adenosine emerges as a highly promising non-invasive biomarker with superior diagnostic accuracy compared to CA19-9.

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Multi-omics analysis of extracellular vesicle cargo in cancer
Areti Georgiadi, Jarne Pauwels, Katleen De Preter, Kris Gevaert
Trends in Cancer.2026;[Epub] CrossRef

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Genitourinary cancer

Efficacy and Safety of Ifosfamide and Mesna in Metastatic Castration-Resistant Prostate Cancer after Taxane-Based Chemotherapy and Novel Hormonal Therapy Failure: Chang Gon Kim, Yeo Gyeong Ko, Jongjin Yoon, Chung Lee, Seung Hoon Beom, Young-Deuk Choi, Woong Kyu Han, Won Sik Ham, Hyunho Han, Jongsoo Lee, Ji Eun Heo, Daeseong Kim, Eun Sil Baek, Sangwoo Kim, Minsun Jung, Sang Joon Shin; Cancer Res Treat. 2026;58(2):603-612. Published online June 9, 2025; DOI: https://doi.org/10.4143/crt.2025.155

Abstract PDF Supplementary Material PubReader ePub: Purpose
Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789).
Materials and Methods
Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m² and mesna 1,500 mg/m² on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA₅₀) or >90% (PSA₉₀), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed.
Results
A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS.
Conclusion
Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

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Review Article

The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine: Jong Hyuk Yun, Yoon Young Choi, Jae-Ho Cheong; Cancer Res Treat. 2025;57(3):621-634. Published online January 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1222

Abstract PDF PubReader ePub

Although gastric cancer remains a significant global health burden, its treatment strategies vary across different geographical regions, leading to distinct guidelines. In Asia, particularly in Korea, D2 gastrectomy followed by adjuvant chemotherapy has been established as the standard treatment for stage II/III gastric cancer based on landmark clinical trials. However, this “one-size-fits-all” approach requires refinement as emerging evidence suggests heterogeneous outcomes even within the same stage. This review discusses the evolving landscape of adjuvant treatment in gastric cancer, emphasizing the transition towards precision medicine. Recent molecular characterization of gastric cancer has revealed distinct subtypes with varying prognoses and chemotherapy responses, exemplified by the favorable outcomes of microsatellite instability–high tumors without adjuvant chemotherapy. Additionally, clinical factors including sub-stages within stage II/III, patient performance status, comorbidities, and personal preferences should be considered in treatment decisions. The integration of these molecular and clinical factors, along with shared decision-making between physicians and patients, represents a crucial step toward personalized treatment approaches. Looking ahead, the field is poised for further evolution with the emergence of immune checkpoint inhibitors, growing evidence for neoadjuvant chemotherapy in selected cases, and the potential of circulating tumor DNA as a biomarker for minimal residual disease. This comprehensive approach to treatment decision-making, considering both tumor biology and patient factors, will be essential for realizing precision medicine in gastric cancer care.

Citations

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From Control to Conversion: Optimizing Systemic Therapy for Curative-Intent Conversion Surgery in Metastatic Gastric Cancer
Hye Sook Han, Sun Young Rha
Journal of Gastric Cancer.2026; 26(1): 146. CrossRef
Advances in Nano-Enabled Biosensing Technology for Gastric Cancer Diagnosis: Mechanistic Insights and Translational Perspectives
Anjali Yadav, Arzoo Saini, Neeraj Dilbaghi, Neelam Yadav
Critical Reviews in Analytical Chemistry.2026; : 1. CrossRef
A Nomogram Integrating HOXA9 Expression and Clinicopathological Factors for Predicting Postoperative Recurrence in Gastric Cancer: A Single-Center Retrospective Study
Jianze Weng, Jingwen Ying, Minming Xia, Yijie Xie
OncoTargets and Therapy.2026; Volume 19: 1. CrossRef
Precision oncology in gastric cancer: navigating molecular subtypes, therapeutic targets, and future horizons
Yanyun Hong, Xiaodong Wang, Hang Yu, Xiaosun Liu, Chao Tang
Cellular Oncology.2026;[Epub] CrossRef
Preoperative albumin-bilirubin grade combined with sarcopenia predicts long-term outcomes after laparoscopic gastrectomy for advanced gastric cancer
Shuangshuang Hou, Yang Yu, Nanbo Li, Wenjing Yu, Zhiyuan Dai, He Li, Lianyi Guo, Jiajun Yin, Ju Wu
BMC Gastroenterology.2025;[Epub] CrossRef
Dynamic postoperative prognosis and follow-up optimization for gastric cancer patients after neoadjuvant therapy: a multicenter retrospective study
Qing Zhong, Zhi-Quan Zhang, Kai-Ning Ye, Min-Xian Zhuang, Yu-Qin Sun, Zhi-Xin Shang-Guan, Dong Wu, Cai-Ming Weng, Meng-Qi Xue, Tao-Yuan Qiu, Yi Li, Yu-Bin Ma, Fang-Hui Ding, Yong-Hong Wang, Shi-Chao Wu, Bao-Long Li, Wei Zhao, Ji-Yun Zhu, Jun-Hua Yu, Ju Wu
Gastric Cancer.2025; 28(6): 1260. CrossRef

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Original Articles

General

Target-Enhanced Whole-Genome Sequencing Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel: Sangmoon Lee, Jin Roh, Jun Sung Park, Islam Oguz Tuncay, Wonchul Lee, Jung-Ah Kim, Brian Baek-Lok Oh, Jong-Yeon Shin, Jeong Seok Lee, Young Seok Ju, Ryul Kim, Seongyeol Park, Jaemo Koo, Hansol Park, Joonoh Lim, Erin Connolly-Strong, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn, Hyun Woo Lee, Seokhwi Kim, Jang-Hee Kim, Minsuk Kwon; Cancer Res Treat. 2025;57(2):350-361. Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.114

Abstract PDF Supplementary Material PubReader ePub

Purpose
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS.
Materials and Methods
This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches.
Results
TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making.
Conclusion
TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Citations

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Whole-genome landscapes of 1,364 breast cancers
Ryul Kim, Jonghan Yu, Joonoh Lim, Brian Baek-Lok Oh, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung Joo Chae, Ji-Yeon Kim, Ga Eun Park, Bong Joo Kang, Pill Sun Paik, Soo Yeon Bae, Chang Ik Yoon, Young Joo Lee, Dooreh Kim, Kabsoo Shin, Ji Eun Lee, Jun Ka
Nature.2026; 649(8099): 1282. CrossRef
Pan-Cancer Targeted Sequencing Reveals Genomic Heterogeneity and Prognostic Subgroups in Urothelial Bladder Cancer
Dimitar Ugrinovski, Skender Saidi, Viktor Stankov, Martina Ambardjieva, Slavica Josifovska, Anne-Katrin Koehler, Joerg Gabert, Sasho Panov
Cancers.2026; 18(6): 1026. CrossRef

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CNS cancer

Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients: Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon; Cancer Res Treat. 2025;57(2):378-386. Published online September 11, 2024; DOI: https://doi.org/10.4143/crt.2024.680

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods
This multi-institutional retrospective study included patients aged ≥ 65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results
A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3 to 149.9 months), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: hazard ratio [HR], 1.52; p < 0.001 and CFRT+TMZ vs. radiotherapy alone: HR, 2.52; p < 0.001). In a combined analysis with the NOA-08 and Nordic trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p < 0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion
CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

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Hypofractionated vs. conventional fractionated radiotherapy in the temozolomide era for elderly patients with glioblastoma: a systematic review and meta-analysis by the Korean Society for Neuro-Oncology
Eunji Kim, Hye In Lee, Tae Hoon Roh, Young Zoon Kim, Do Hoon Lim, Se Jin Cho, Kihwan Hwang, Chan Woo Wee
Journal of Neuro-Oncology.2026;[Epub] CrossRef
Comparative analysis of outcome, recurrence patterns, and dosimetry in glioblastoma patients treated according to RTOG versus EORTC contouring guidelines
Gero Wieger, Patricia Meixner, Alicia Bicu, Frederik M Glatting, Frank A Giordano, Arne Mathias Ruder
Neuro-Oncology Practice.2026; 13(2): 301. CrossRef
Efficacy and safety of hypofractionated radiotherapy for melanoma brain metastases: a retrospective study
Yacheng Wang, Heng Zhang, Zibo Tang, Dehua Kang, Weihao Xie, Xiaoshi Zhang, Lixia Lu
Frontiers in Oncology.2026;[Epub] CrossRef
Hypofractionated MR-guided radiotherapy for glioblastoma: Institutional online adaptive workflow using MR-linac
Alonso La Rosa, Giorgia Yang, Beatriz Moreno, Laura Zaragoza, Inmaculada Navarro, Concepción Huertas, Carlos Ferrer, Raúl Matute, Ana Castaño, Patricia Arroyo, Beatriz Sánchez, Daniel Camacho, Silvia Lago, Juan Camilo Urrea, Moisés Sáez, Rosa Morera
Medical Dosimetry.2026;[Epub] CrossRef

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Breast cancer

A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong; Cancer Res Treat. 2024;56(4):1113-1125. Published online May 10, 2024; DOI: https://doi.org/10.4143/crt.2024.100

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

Citations

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Revolutionizing early detection of TNBC: The rise of non-invasive biomarkers and next-gen diagnostic strategies
Aqsa Ashraf, Syeda Zainab Amir, Laiba Jahangir, Emma Daniel, Muhammad Mustafa
Critical Reviews in Oncology/Hematology.2026; 218: 105107. CrossRef
Artificial Intelligence in Triple-Negative Breast Cancer: Applications in Diagnosis, Treatment Response, and Prognosis
Ziyu Fu, Xiaofei Huo, Andrew B. Jing, Jingfei Ma, Gaiane M. Rauch
Diagnostics.2026; 16(5): 671. CrossRef
Integrating multi-omics and artificial intelligence for personalized breast cancer management: A guide to clinicians
Hussein Sabit, Amit K. Yadav, Siamak Salimy, Amr Sakr, Shaimaa Abdel-Ghany, Alhassan Soliman Wadan, Amany I. Alqosaibi, Rawan Rashwan, Yara Saad AlGosaibi, Mashael Mashal Alnamshan, Jawaher Almulhim, Nouf K. Alaqeel, Borros Arneth
Cancer Letters.2026; 649: 218468. CrossRef
Development of predictive models for the prognosis of triple-negative breast cancer using multiple transcriptomic analyses
Suhyun Hwangbo, Yoojin Choi, Jae Yong Ryu, Julie Decock
PLOS One.2026; 21(5): e0348414. CrossRef
A 20-feature radiomic signature of triple-negative breast cancer identifies patients at high risk of death
Humaira Noor, Yuanning Zheng, Adam B. Mantz, Ryle Zhou, Andrew Kozlov, Wendy B. DeMartini, Shu-Tian Chen, Satoko Okamoto, Debra M. Ikeda, Melinda L. Telli, Allison W. Kurian, James M. Ford, Shaveta Vinayak, Mina Satoyoshi, Vishal Joshi, Sarah A. Mattonen,
npj Breast Cancer.2025;[Epub] CrossRef
Gadd45B Deficiency Drives Radio-Resistance in BRAFV600E-Mutated Differentiated Thyroid Cancer by Disrupting Iodine Metabolic Genes
Shan Jiang, Zhiwen Hong, Qianjiang Wu, Rouhan A, Zhaobo Wang, Xue Guan, Xinghua Wang, Ari A. Kassardjian, Yali Cui, Tengchuang Ma
Cancers.2025; 17(19): 3201. CrossRef
A systems biology approach to unveil shared therapeutic targets and pathological pathways across major human cancers
Aftab Alam, Mohd Faizan Siddiqui, Rifat Hamoudi, Uday Kishore, Maria J. Fernandez-Cabezudo, Basel K. Al-Ramadi
Computational and Structural Biotechnology Journal.2025; 27: 5459. CrossRef
Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database
Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan, Masakazu Yashiro
Genes.2024; 15(6): 792. CrossRef

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Review Article

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design: Hyerim Ha, Hee Yeon Lee, Jee Hyun Kim, Do Yeun Kim, Ho Jung An, SeungJin Bae, Hye-sung Park, Jin Hyoung Kang; Cancer Res Treat. 2024;56(4):991-1013. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.128

Abstract PDF Supplementary Material PubReader ePub

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

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Original Articles

Genitourinary cancer

Early Plasma Circulating Tumor DNA as a Potential Biomarker of Disease Recurrence in Non-metastatic Prostate Cancer: Xiaochen Fei, Xinxing Du, Yiming Gong, Jiazhou Liu, Liancheng Fan, Jiayi Wang, Yanqing Wang, Yinjie Zhu, Jiahua Pan, Baijun Dong, Wei Xue; Cancer Res Treat. 2023;55(3):969-977. Published online March 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1557

Abstract PDF Supplementary Material PubReader ePub

Purpose
In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.
Materials and Methods
This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression.
Results
Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence.
Conclusion
Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Citations

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Liquid Biopsy in Non-Metastatic Prostate Cancer: Clinical Evidence and Future Directions
Maria Chiara Sighinolfi, Giuseppe Pallotta, Marzia Del Re, Koosha Moosavi, Or Schubert, Francesco Rossi, Filippo Gavi, Simone Assumma, Enrico Panio, Angelo Totaro, Filippo Turri, Mauro Ragonese, Nazario Foschi, Pierluigi Russo, Ela Patel, Carlo Gandi, Giu
Cancers.2026; 18(5): 800. CrossRef
Letter to the Editor: “Dynamic risk stratification - guided management of medullary thyroid carcinoma: integrating surgical precision with RET-targeted therapies and molecular surveillance”
Lei Tang
International Journal of Surgery.2026; 112(2): 5424. CrossRef
Using ctDNA to Inform Adjuvant Therapy for Urologic Malignancies
Rajvi Goradia, Taylor Goodstein, Debasish Sundi, Akshay Sood, Shawn Dason, Eric A. Singer
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Method development for pancreatic and ovarian cancer baseline ctDNA detection and measurable residual disease monitoring
Tim Alexander Steiert, Philipp M. Altrock, Axel Künstner, Vishal Dixit, Burkhard Brandt, Pamela Pinzani, Hauke Busch, Andre Franke, Michael Forster
Open Research Europe.2026; 6: 87. CrossRef
Method development for pancreatic and ovarian cancer baseline ctDNA detection and measurable residual disease monitoring
Tim Alexander Steiert, Philipp M. Altrock, Axel Künstner, Vishal Dixit, Burkhard Brandt, Pamela Pinzani, Hauke Busch, Andre Franke, Michael Forster
Open Research Europe.2026; 6: 87. CrossRef
Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer
Angela Yee, Jim Smith, Rajiv Kumar, Akash Sali, Euan J. Rodger, Aniruddha Chatterjee
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Minimal residual disease as a target for liquid biopsy in patients with solid tumours
Klaus Pantel, Catherine Alix-Panabières
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Marius E. Mayerhoefer, Andreas Kienzle, Sungmin Woo, Hebert Alberto Vargas
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Lilia Bardoscia, Angela Sardaro, Mariagrazia Quattrocchi, Paola Cocuzza, Elisa Ciurlia, Ilaria Furfaro, Maria Antonietta Gilio, Marcello Mignogna, Beatrice Detti, Gianluca Ingrosso
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Circulating Tumor DNA in Prostate Cancer: A Dual Perspective on Early Detection and Advanced Disease Management
Stepan A. Kopytov, Guzel R. Sagitova, Dmitry Y. Guschin, Vera S. Egorova, Andrei V. Zvyagin, Alexey S. Rzhevskiy
Cancers.2025; 17(15): 2589. CrossRef
Current Status and Future Perspectives of Molecular Residual Disease Testing in Genitourinary Cancers
Taigo Kato, Shugo Yajima, Yoshiaki Nakamura, Shin Kobayashi, Hideaki Miyake
International Journal of Urology.2025; 32(12): 1735. CrossRef
Circulating Tumor DNA as a Biomarker for Precision Medicine in Prostate Cancer: A Systematic Review
Nouhaila Chanhih, Abdelilah Laraqui, Salma Hassine, Ahmed Ameur, Larbi Hamedoun, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Idriss Lahlou Amine, Khalid Ennibi, Abdelaziz Benjouad, Lamiae Belayachi
International Journal of Molecular Sciences.2025; 26(22): 11049. CrossRef
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Tatiana M. Zavarykina, Irina V. Pronina, Polina S. Mazina, Svetlana V. Khokhlova, Gennady T. Sukhikh
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Yuanshe Huang, Jingxin Mao, Xiaobing Li
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Joe Youssef, Amani Yehya, Zahraa Salhab, Ricardo Bitar, Fatima Ghamlouche, Hisham F Bahmad, Wassim Abou-Kheir
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Hematologic malignancy

Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas: Seok Jin Kim, Yeon Jeong Kim, Sang Eun Yoon, Kyung Ju Ryu, Bon Park, Donghyun Park, Duck Cho, Hyun-Young Kim, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Won Seog Kim; Cancer Res Treat. 2023;55(1):291-303. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2022.017

Abstract PDF Supplementary Material PubReader ePub

Purpose
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

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Ang Li, Hao Hu, Xuefei Liu, Na Xiao, Feizhen Wu, Miaoxia He
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Abdurraouf Mokhtar Mahmoud, Jasmitaben Prakashbhai Touti, Syed Rubina Zaidi, Ahad Ahmed Kodipad, Clara Deambrogi
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Mutation Profiling, Efficacy Monitoring, and Prognosis Evaluation Using Circulating Tumor DNA in Peripheral T‐Cell Lymphoma: A Prospective, Multicenter, Observational Study
Zhao Donglu, Song Yuqin, Qin Jiayue, Tong Hongyan, Ding Kaiyang, Cai Qingqing, Huang Huiqiang, Wu Lili, Jing Hongmei, Zhang Liling, Qian Wenbin, Bai Ou, Cao Shanbo, Jin Jie, Zhu Jun, Ma Jun
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Liquid biopsy for molecular profiling in cutaneous T-cell lymphoma: a pilot feasibility study
Yoni Sacknovitz, Anna Sarah Erem, Joshua A. Kent, Maher Albitar, Tatyana Feldman, Barbara Pro, Seda S. Tolu, Alejandro A. Gru, Larisa Geskin
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Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
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Personalized Immunotherapy for T Cell Lymphomas: From Immune Escape to Precision Therapeutics
Joshua M. L. Casan, Xiao Jing Ong, Carrie van der Weyden, Costas K. Yannakou, Joe Zhu, Criselle D’Souza, Paul Neeson, H. Miles Prince
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Association of PET4 response with outcomes of BV-CHP vs CHOP in the ECHELON-2 trial in CD30+ peripheral T-cell lymphoma
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Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
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Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
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Gastrointestinal cancer

Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer: Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim; Cancer Res Treat. 2022;54(4):1175-1190. Published online January 12, 2022; DOI: https://doi.org/10.4143/crt.2021.1133

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification.

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Yang An, Jiaolin Zhou, Lan Su, Lin Cong, Xinxin Mao, Bo Chen, Yuhua Gong, Yaping Xu, Han Chen, Chentong Wang, Guole Lin, Huanwen Wu
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Fanqin Zhang, Chao Wu, Jingyuan Zhang, Zhihong Huang, Antony Stalin, Yiyan Zhai, Shuqi Liu, Jiarui Wu
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Genitourinary cancer

Next-generation Proteomics-Based Discovery, Verification, and Validation of Urine Biomarkers for Bladder Cancer Diagnosis: Jungyo Suh, Dohyun Han, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak, Chang Wook Jeong; Cancer Res Treat. 2022;54(3):882-893. Published online October 9, 2021; DOI: https://doi.org/10.4143/crt.2021.642

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to identify, verify, and validate a multiplex urinary biomarker-based prediction model for diagnosis and surveillance of urothelial carcinoma of bladder, using high-throughput proteomics methods.
Materials and Methods
Label-free quantification of data-dependent and data-independent acquisition of 12 and 24 individuals was performed in each of the discovery and verification phases using mass spectrometry, simultaneously using urinary exosome and proteins. Based on five scoring system based on proteomics data and statistical methods, we selected eight proteins. Enzyme-linked immunosorbent assay on urine from 120 patients with bladder mass lesions used for validation. Using multivariable logistic regression, we selected final candidate models for predicting bladder cancer.
Results
Comparing the discovery and verification cohorts, 38% (50/132 exosomal differentially expressed proteins [DEPs]) and 44% (109/248 urinary DEPs) are consistent at statistically significance, respectively. The 20 out of 50 exosome proteins and 27 out of 109 urinary proteins were upregulated in cancer patients. From eight selected proteins, we developed two diagnostic models for bladder cancer. The area under the receiver operating characteristic curve (AUROC) of two models were 0.845 and 0.842, which outperformed AUROC of urine cytology.
Conclusion
The results showed that the two diagnostic models developed here were more accurate than urine cytology. We successfully developed and validated a multiplex urinary protein-based prediction, which will have wide applications for the rapid diagnosis of urothelial carcinoma of the bladder. External validation for this biomarker panel in large population is required.

Citations

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Extracellular vesicles in tumor microenvironment modulation and clinical diagnosis
Huan Liu, Dong Niu, Tong-Yao Yu, Yu-Hua Wang, Kun-Lin Ran, Yan-Hua Liu, Da-Chuan Yin, Chen-Yan Zhang
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Divya Pandey, Vineeta Tiwari, Dipanjana Ghosh
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Lung and Thoracic cancer

Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung; Cancer Res Treat. 2022;54(2):424-433. Published online July 7, 2021; DOI: https://doi.org/10.4143/crt.2021.583

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Citations

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Xinyi Shi, Yang Wang, Nan Yao, Bowen Xue, Lei Guo, Liming Xu, Changbin Zhu, Guiping Qin, Jianming Ying, Yutao Liu, Weihua Li
Molecular Biomedicine.2026;[Epub] CrossRef
Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
Chuanhao Tang, Zaizai Dong, Shi Yan, Bing Liu, Zhiying Wang, Long Cheng, Feng Liu, Hong Sun, Yimeng Du, Lu Pan, Yuhao Zhou, Zhiyuan Jin, Libo Zhao, Nan Wu, Lingqian Chang, Xiaojie Xu
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Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
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The DDR-immune fitness score: a biomarker for guiding parp and immunotherapy synergy in extensive-stage small cell lung cancer
Yinxu Zhang, Xiaoyang Chen, Dai Wang, Xuan Zhou, Yuxi Wang, Guangyu Zhang, Xiaomei Liu
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Junming Chen, Jiayi Zhan, Ying Zhou
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Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)
Mo Cheng, Xiufeng Zheng, Jing Wei, Ming Liu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef

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Head and Neck Cancer

Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12: Yun-Gyoo Lee, Hyun Chang, Bhumsuk Keam, Sang Hoon Chun, Jihyun Park, Keon Uk Park, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, Keun-Wook Lee, Hye Ryun Kim, Sung-Bae Kim, Myung-Ju Ahn, In Gyu Hwang; Cancer Res Treat. 2021;53(3):671-677. Published online December 7, 2020; DOI: https://doi.org/10.4143/crt.2020.824

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.

Citations

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Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review
JiaJu Xu, ChunXiao Ni, Lidong Qin, Ping Wang, JiaJu Xu
Clinical and Translational Oncology.2026;[Epub] CrossRef
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Angeline A. Truong, Savinnie Ho, Rex H. Lee, Xin Wu, Hyunseok Kang, Ivan H. El‐Sayed, Jonathan R. George, Chase M. Heaton, Ilya Likhterov, Mary Jue Xu, Patrick K. Ha, Alain P. Algazi, Katherine C. Wai
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Neutrophil‐to‐Lymphocyte Ratio and Pembrolizumab Outcomes in Oral Cavity Squamous Cell Carcinoma
Angeline A. Truong, Rex H. Lee, Xin Wu, Alain P. Algazi, Hyunseok Kang, Ivan H. El‐Sayed, Jonathan R. George, Chase M. Heaton, William R. Ryan, Yena Jeon, Mi‐Ok Kim, Patrick K. Ha, Katherine C. Wai
Otolaryngology–Head and Neck Surgery.2025; 172(2): 548. CrossRef
Risk Factors for Progressive Disease After Immune Checkpoint Inhibitor Therapy in Head and Neck Squamous Cell Carcinoma
Seo Yoon Jang, Yun‐Gyoo Lee, Sang Hoon Chun, Ji Hyun Park, Keon Uk Park, Hyun Chang, Keun‐Wook Lee, Hye Ryun Kim, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, In Gyu Hwang, Myung‐Ju Ahn, Sung‐Bae Kim, Bhumsuk Keam
Head & Neck.2025; 47(6): 1621. CrossRef
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Kun Gao, Zhigong Wei, Zheran Liu, Yiyan Pei, Huilin Li, Ge Song, Jin Xiang, Junyou Ge, Yan Qing, Youneng Wei, Ping Ai, Ye Chen, Xingchen Peng
Head & Neck.2025; 47(7): 1928. CrossRef
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Marianna Caterino, Giorgio Lo Giudice, Vincenzo Damiano, Francesco Perri, Guido Giordano, Davide Ciardiello, Aurora Mirabile, Mario Pirozzi, Andrea Pietro Sponghini, Vincenzo Ricci, Liliana Montella, Raffaele Addeo, Francesca Vignani, Vincenzo Famiglietti
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Kazufumi Obata, Satoshi Kano, Akira Ohkoshi, Akito Kakiuchi, Takahiro Inoue, Jun Taguchi, Ai Tagawa, Daisuke Matsushita, Jun Miyaguchi, Tentaro Endo, Ryo Ishii, Kazue Ito, Eiichi Ishida, Takahiro Suzuki, Naoto Araki, Tomotaka Kawase, Kenichi Takano
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Lei Liu, Qiang Liu
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Quan Wang, Xiangzhi Yin, Shengxia Wang, Haijun Lu
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Dong Hyun Kim, Seo Yoon Jang, Bhumsuk Keam
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Piero Giuseppe Meliante, Federica Zoccali, Marco de Vincentiis, Massimo Ralli, Carla Petrella, Marco Fiore, Antonio Minni, Christian Barbato
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Catherine T. Haring, Lulia A. Kana, Sarah M. Dermody, Collin Brummel, Jonathan B. McHugh, Keith A. Casper, Steven B. Chinn, Kelly M. Malloy, Michelle Mierzwa, Mark E. P. Prince, Andrew J. Rosko, Jennifer Shah, Chaz L. Stucken, Andrew G. Shuman, J. Chad Br
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Camil Ciprian Mireștean, Mihai Cosmin Stan, Michael Schenker, Constantin Volovăț, Simona Ruxandra Volovăț, Dragoș Teodor Petru Iancu, Roxana Irina Iancu, Florinel Bădulescu
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Sagar Dholariya, Ragini D. Singh, Amit Sonagra, Dharamveer Yadav, Bhairavi N. Vajaria, Deepak Parchwani
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Khalil Choucair, Caroline Nebhan, Alessio Cortellini, Stijn Hentzen, Yinghong Wang, Cynthia Liu, Raffaele Giusti, Marco Filetti, Paolo Antonio Ascierto, Vito Vanella, Domenico Galetta, Annamaria Catino, Nour Al-Bzour, Azhar Saeed, Ludimila Cavalcante, Pam
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Dengxiong Kang, Siping Liu, Xin Yuan, Shenxiang Liu, Zhengrong Zhang, Zhilian He, Xudong Yin, Haiyan Mao
Journal of Cancer Research and Clinical Oncology.2023; 149(20): 18215. CrossRef
Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio during immune checkpoint inhibitor treatment in recurrent or metastatic head and neck squamous cell carcinoma patients
Jun-Liang Li, Tsai-Ling Hsieh, Ming-Che Ou, Frank Cheau-Feng Lin, Stella Chin-Shaw Tsai
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Yukinori Takenaka, Ryohei Oya, Norihiko Takemoto, Hidenori Inohara
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25 Crossref

Breast cancer

Upregulated N6-Methyladenosine RNA in Peripheral Blood: Potential Diagnostic Biomarker for Breast Cancer: Han Xiao, Xiaobo Fan, Rui Zhang, Guoqiu Wu; Cancer Res Treat. 2021;53(2):399-408. Published online October 27, 2020; DOI: https://doi.org/10.4143/crt.2020.870

Abstract PDF Supplementary Material PubReader ePub

Purpose
An effective biomarker for the diagnosis of breast cancer (BC) and benign breast diseases (BBD) is crucial for improving the prognosis. We investigated whether N6-methyladenosine (m⁶A) can be a diagnostic biomarker of BC.
Materials and Methods
We detected the contents of peripheral blood m⁶A in 62 patients with BC, 41 patients with BBD, and 41 normal controls (NCs) using the colorimetric method. The relative expression of the m⁶A regulated genes methyltransferase-like 14 (METTL14) and fat mass and obesity-associated (FTO) was analyzed using quantitative real-time polymerase chain reaction.
Results
m⁶A in peripheral blood RNA was significantly higher in patients with BC than that in patients with BBD (p < 0.001) or the NCs (p < 0.001). m⁶A was closely associated with the disease stage (from stage 0 to stage I-IV, p=0.003). The receiver operating characteristic curve of m⁶A contained an area under the curve (AUC) value of 0.887 in BC, which was greater than that of carcinoembryonic antigen (CEA) or carbohydrate antigen 153 (CA153). The combination of m⁶A, CEA, and CA153 improved the AUC to 0.914. The upregulated and downregulated mRNA expression of METTL14 and FTO, respectively, might contribute to the increase of m⁶A in patients with BC. m⁶A combined with METTL14 and FTO improved the AUC to 0.929 with a specificity of 97.4% in the peripheral blood of patients with BC.
Conclusion
The peripheral blood RNA of m⁶A might be a valuable biomarker for the diagnosis of BC.

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Gastrointestinal cancer

Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma Incorporating Hematological Biomarkers: Yingjia Wu, Jinbin Chen, Lei Zhao, Qiaoqiao Li, Jinhan Zhu, Hong Yang, Suping Guo, Mian Xi; Cancer Res Treat. 2021;53(1):172-183. Published online September 4, 2020; DOI: https://doi.org/10.4143/crt.2020.594

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics.
Materials and Methods
Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated.
Results
Absolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78).
Conclusion
Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×10⁹/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

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A composite immune-nutritional and tumor marker score predicts outcomes in LA-ESCC treated with neoadjuvant chemoimmunotherapy and surgery
Yiwei Fan, Jiang Zhou, Xiaotian Liu, Qianhe Ren, Shichun Lu, Weiguo Jin
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Development of a predictive model for pathological complete response following neoadjuvant immunotherapy and chemotherapy in locally advanced resectable esophageal squamous cell carcinoma
Yilei Zhang, Hounai Xie, Deguo Zhang, Yujuan Liu, Shuaiming Fu, Yongkui Yu, Wei Ma
World Journal of Surgical Oncology.2026;[Epub] CrossRef
Exploratory analysis of serial pan-immune-inflammation value and its early dynamics during neoadjuvant chemotherapy as a predictor of complete cytoreduction at interval debulking surgery in advanced ovarian cancer: a retrospective cohort study
Hao Su, Mingle Tian, Yongxue Wang, Yuan Li, Ying Shan, Ying Jin, Fengzhi Feng, Tao Wang
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The predictive role of hematologic indicators in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemoimmunotherapy
Zhuoya Xie
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The Predictive Value of Red Cell Distribution Width in End-Stage Colorectal Cancers’ 6-Month Palliative Chemotherapy Response—A Single Center’s Experience
Maciej Jankowski, Krystyna Bratos, Joanna Wawer, Tomasz Urbanowicz
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Perioperative outcomes of neoadjuvant chemotherapy plus camrelizumab versus neoadjuvant chemotherapy plus tislelizumab for locally advanced esophageal squamous cell cancer: a real-world retrospective study
Qi Zhao, Yusen Yuan, Tongxin Xu, Ningning Yan, Fei Li, Juntao Lu, Ming He, Zhaoyang Yan
Frontiers in Immunology.2025;[Epub] CrossRef
Prognostic value of neutrophil to lymphocyte ratio in patients with esophagus cancer receiving neoadjuvant therapy: a systematic review and meta-analysis
Longwei Ma, Jiaxing He, Ping Li, Long Ma, He Wang, Yanchao Deng
Frontiers in Immunology.2025;[Epub] CrossRef
Pan-immune-inflammation value as a novel predictor of pathological response to neoadjuvant chemotherapy combined with anti-PD-1 therapy in esophageal squamous cell carcinoma: a multicenter real-world retrospective clinical study
Jiang-shan Huang, Qi-hong Zhong, Gang Wang, Zi-lu Tang, Bing-Lin Shen, Wei-nan Liu, Fei-long Guo, Jing-yu Wu, Zhen-yang Zhang, Jiang-bo Lin
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CT-based deep learning radiomics and hematological biomarkers in the assessment of pathological complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma: A two-center study
Meng Zhang, Yukun Lu, Hongfu Sun, Chuanke Hou, Zichun Zhou, Xiao Liu, Qichao Zhou, Zhenjiang Li, Yong Yin
Translational Oncology.2024; 39: 101804. CrossRef
A machine learning approach using 18F-FDG PET and enhanced CT scan-based radiomics combined with clinical model to predict pathological complete response in ESCC patients after neoadjuvant chemoradiotherapy and anti-PD-1 inhibitors
Wei-Xiang Qi, Shuyan Li, Jifeng Xiao, Huan Li, Jiayi Chen, Shengguang Zhao
Frontiers in Immunology.2024;[Epub] CrossRef
Neoadjuvant PD-1 Plus Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma
Ting Qian, Delin Liu, Guochun Cao, Zhipeng Chen, Qin Zhang
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Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma
Guihong Liu, Tao Chen, Xin Zhang, Binbin Hu, Jiayun Yu
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Xing Gao, Hidde C G Overtoom, Ben M Eyck, Shi-Han Huang, Daan Nieboer, Pieter C van der Sluis, Sjoerd M Lagarde, Bas P L Wijnhoven, Yin-Kai Chao, Jan J B van Lanschot
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Yunsong Liu, Zeliang Ma, Yongxing Bao, Xin Wang, Yu Men, Xujie Sun, Feng Ye, Kuo Men, Jianjun Qin, Nan Bi, Liyan Xue, Zhouguang Hui
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Esra KEKİLLİ, Ebru ATASEVER AKKAŞ, Serab UYAR, Emre YEKEDÜZ
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A Novel Predictor of Pathologic Complete Response for Neoadjuvant Immunochemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma
Yalan Yang, Dao Xin, Huike Wang, Lulu Guan, Xiangrui Meng, Taiying Lu, Xiwen Bai, Feng Wang
Journal of Inflammation Research.2023; Volume 16: 1443. CrossRef
Gut microbiome can predict chemoradiotherapy efficacy in patients with esophageal squamous cell carcinoma
Takuma Sasaki, Yasunori Matsumoto, Kentaro Murakami, Satoshi Endo, Takeshi Toyozumi, Ryota Otsuka, Kazuya Kinoshita, Jie Hu, Shinichiro Iida, Hiroki Morishita, Yuri Nishioka, Akira Nakano, Masaya Uesato, Hisahiro Matsubara
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Wei‐Xiang Qi, Xiaoyan Wang, Chengqiang Li, Shuyan Li, Huan Li, Feifei Xu, Jiayi Chen, Shengguang Zhao, Hecheng Li
Thoracic Cancer.2023; 14(17): 1556. CrossRef
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Lian-Qiang Han, Ting-Ting Cui, Nian-Jun Xiao, Wen Li
Journal of Cancer Research and Clinical Oncology.2023; 149(17): 15413. CrossRef
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Dan He, Shulan Du, Songyuan He, Hao Song, Bo Pu, Guojun Zhang, Chuan Yang
Medicine.2023; 102(49): e36554. CrossRef
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Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
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Impact of Platelets to Lymphocytes Ratio and Lymphocytes during Radical Concurrent Radiotherapy and Chemotherapy on Patients with Nonmetastatic Esophageal Squamous Cell Carcinoma
Yaotian Zhang, Ning Han, Xue Zeng, Chaonan Sun, Shichen Sun, Xinchi Ma, Yanyu Zhang, Zhuang Liu, Zilan Qin, Hong Guo, Yubing Li, Na Zhang, Bruno Vincenzi
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Serum Anti-BRAT1 is a Common Molecular Biomarker for Gastrointestinal Cancers and Atherosclerosis
Liubing Hu, Jiyue Liu, Hideaki Shimada, Masaaki Ito, Kazuo Sugimoto, Takaki Hiwasa, Qinghua Zhou, Jianshuang Li, Si Shen, Hao Wang
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Noel E Donlon, Maria Davern, Fiona O’Connell, Andrew Sheppard, Aisling Heeran, Anshul Bhardwaj, Christine Butler, Ravi Narayanasamy, Claire Donohoe, James J Phelan, Niamh Lynam-Lennon, Margaret R Dunne, Stephen Maher, Jacintha O’Sullivan, John V Reynolds,
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Jifeng Feng, Liang Wang, Xun Yang, Qixun Chen, Xiangdong Cheng
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The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy
Jin Zhou, Hai-Ping Lin, Xin Xu, Xiao-Hang Wang, Ling Rong, Yao Zhang, Lei Shen, Lei Xu, Wei-Ting Qin, Qing Ye, Xiu-Mei Ma, Yong-Rui Bai
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Gynecologic cancer

Evaluation of Circulating Tumor DNA in Patients with Ovarian Cancer Harboring Somatic PIK3CA or KRAS Mutations: Aiko Ogasawara, Taro Hihara, Daisuke Shintani, Akira Yabuno, Yuji Ikeda, Kenji Tai, Keiichi Fujiwara, Keisuke Watanabe, Kosei Hasegawa; Cancer Res Treat. 2020;52(4):1219-1228. Published online May 6, 2020; DOI: https://doi.org/10.4143/crt.2019.688

Abstract PDF Supplementary Material PubReader ePub

Purpose
Circulating tumor DNA (ctDNA) is an attractive source for liquid biopsy to understand molecular phenotypes of a tumor non-invasively, which is also expected to be both a diagnostic and prognostic marker. PIK3CA and KRAS are among the most frequently mutated genes in epithelial ovarian cancer (EOC). In addition, their hotspot mutations have already been identified and are ready for a highly sensitive analysis. Our aim is to clarify the significance of PIK3CA and KRAS mutations in the plasma of EOC patients as tumor-informed ctDNA.
Methods
We screened 306 patients with ovarian tumors for somatic PIK3CA or KRAS mutations. A total of 85 EOC patients had somatic PIK3CA and/or KRAS mutations, and the corresponding mutations were subsequently analyzed using a droplet digital polymerase chain reaction in their plasma.
Results
The detection rates for ctDNA were 27% in EOC patients. Advanced stage and positive peritoneal cytology were associated with higher frequency of ctDNA detection. Preoperative ctDNA detection was found to be an indicator of outcomes, and multivariate analysis revealed that ctDNA remained an independent risk factor for recurrence (p=0.010). Moreover, we assessed the mutation frequency in matched plasma before surgery and at recurrence from 17 patients, and found six patients had higher mutation rates in cell-free DNA at recurrence compared to that at primary diagnosis.
Conclusion
The presence of ctDNA at diagnosis was an indicator for recurrence, which suggests potential tumor spread even when tumors were localized at the time of diagnosis.

Citations

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Liquid biopsy in gynecological cancers: a translational framework from molecular insights to precision oncology and clinical practice
Canio Martinelli, Alfredo Ercoli, Giuseppe Vizzielli, Sharon Raffaella Burk, Maria Cuomo, Vrunda Satasiya, Housem Kacem, Simone Braccia, Giulio Mazzarotti, Irene Miriello, Manuela Nana Tchamou, Stefano Restaino, Martina Arcieri, Alice Poli, Veronica Tius,
Journal of Experimental & Clinical Cancer Research.2025;[Epub] CrossRef
Clinical utility of various liquid biopsy samples for the early detection of ovarian cancer: a comprehensive review
Yueqi Feng, Wanjun Yang, Jingyu Zhu, Shirui Wang, Ningjuan Wu, Hanzhi Zhao, Xiaofeng Yang
Frontiers in Oncology.2025;[Epub] CrossRef
Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis
Cristina Taliento, Giampaolo Morciano, Camilla Nero, Wouter Froyman, Giuseppe Vizzielli, Matteo Pavone, Stefano Salvioli, Mara Tormen, Francesco Fiorica, Gennaro Scutiero, Giovanni Scambia, Carlotta Giorgi, Pantaleo Greco, Paolo Pinton
International Journal of Gynecologic Cancer.2024; : ijgc-2024-005313. CrossRef
DNA methylation marker to estimate ovarian cancer cell fraction
Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
Medical Oncology.2022;[Epub] CrossRef
Detection of ESR1 Mutations in Primary Tumors and Plasma Cell-Free DNA in High-Grade Serous Ovarian Carcinoma Patients
Dimitra Stergiopoulou, Athina Markou, Lydia Giannopoulou, Paul Buderath, Ioanna Balgkouranidou, Nikolaos Xenidis, Stylianos Kakolyris, Sabine Kasimir-Bauer, Evi Lianidou
Cancers.2022; 14(15): 3790. CrossRef
Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer
Christen A. Khella, Gaurav A. Mehta, Rushabh N. Mehta, Michael L. Gatza
Journal of Personalized Medicine.2021; 11(2): 149. CrossRef
Tumor-related mutations in cell-free DNA in pre-operative plasma as a prognostic indicator of recurrence in endometrial cancer
Daisuke Shintani, Taro Hihara, Aiko Ogasawara, Sho Sato, Akira Yabuno, Kenji Tai, Keiichi Fujiwara, Keisuke Watanabe, Kosei Hasegawa
International Journal of Gynecological Cancer.2020; 30(9): 1340. CrossRef

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Gastrointestinal cancer

A Multi-cohort Study of the Prognostic Significance of Microsatellite Instability or Mismatch Repair Status after Recurrence of Resectable Gastric Cancer: Ji Yeong An, Yoon Young Choi, Jeeyun Lee, Woo Jin Hyung, Kyoung-Mee Kim, Sung Hoon Noh, Min-Gew Choi, Jae-Ho Cheong; Cancer Res Treat. 2020;52(4):1153-1161. Published online May 4, 2020; DOI: https://doi.org/10.4143/crt.2020.173

Abstract PDF Supplementary Material PubReader ePub

Purpose
High microsatellite instability (MSI) is related to good prognosis in gastric cancer. We aimed to identify the prognostic factors of patients with recurrent gastric cancer and investigate the role of MSI as a prognostic and predictive biomarker of survival after tumor recurrence.
Materials and Methods
This retrospective cohort study enrolled patients treated for stage II/III gastric cancer who developed tumor recurrence and in whom the MSI status or mismatch repair (MMR) status of the tumor was known. MSI status and the expression of MMR proteins were evaluated using polymerase chain reaction and immunohistochemical analysis, respectively.
Results
Of the 790 patients included, 64 (8.1%) had high MSI status or MMR deficiency. The tumor-node-metastasis stage, type of recurrence, Lauren classification, chemotherapy after recurrence, and interval to recurrence were independently associated with survival after tumor recurrence. The MSI/MMR status and receiving adjuvant chemotherapy were not associated with survival after recurrence. In a subgroup analysis of patients with high MSI or MMR-deficient gastric cancer, those who did not receive adjuvant chemotherapy had better treatment response to chemotherapy after recurrence than those who received adjuvant chemotherapy.
Conclusion
Patients with high MSI/MMR-deficient gastric cancer should be spared from adjuvant chemotherapy after surgery, but aggressive chemotherapy after recurrence should be considered. Higher tumor-node-metastasis stage, Lauren classification, interval to recurrence, and type of recurrence are associated with survival after tumor recurrence and should thus be considered when establishing a treatment plan and designing clinical trials targeting recurrent gastric cancer.

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Trends and hot spots in research on the prognostic value of gastric cancer biomarkers in the context of the Lauren classification: a bibliometric analysis
Nurbek Kozhakhmetuly Azbergenov, Talshyn Amirkhanqyzy Nurulla, Anar Balkashevna Tulyayeva, Saule Zhumabaevna Akhmetova, Nurgul Meirimovna Kereeva, Saltanat Nurslyamovna Akanova, Dinara Almatovna Zholmukhamedova
Frontiers in Medicine.2025;[Epub] CrossRef
HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients
Shibo Wang, Siyi Zhang, Xiaoxuan Li, Xiangxue Li, Shufen Zhao, Jing Guo, Shasha Wang, Rui Wang, Mengqi Zhang, Wensheng Qiu
Frontiers in Immunology.2024;[Epub] CrossRef
Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis
Li-Hua Zhang, Hui-Qin Zhuo, Jing-Jing Hou, Yang Zhou, Jia Cheng, Jian-Chun Cai
World Journal of Gastrointestinal Oncology.2022; 14(11): 2097. CrossRef
The distinct clinical trajectory, metastatic sites, and immunobiology of microsatellite-instability-high cancers
Shuting Han, Aik Yong Chok, Daniel Yang Yao Peh, Joshua Zhi-Ming Ho, Emile Kwong Wei Tan, Si-Lin Koo, Iain Bee-Huat Tan, Johnny Chin-Ann Ong
Frontiers in Genetics.2022;[Epub] CrossRef
Mismatch Repair Status Characterization in Oncologic Pathology: Taking Stock of the Real-World Possibilities
Roberto Piciotti, Konstantinos Venetis, Elham Sajjadi, Nicola Fusco
Journal of Molecular Pathology.2021; 2(2): 93. CrossRef
The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis
Wen-Long Guan, Yue Ma, Yue-Hong Cui, Tian-Shu Liu, Yan-Qiao Zhang, Zhi-Wei Zhou, Jian-Ying Xu, Li-Qiong Yang, Jia-Yu Li, Yu-Ting Sun, Rui-Hua Xu, Feng-Hua Wang, Miao-Zhen Qiu
Frontiers in Oncology.2021;[Epub] CrossRef
Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis
Gang Hu, Ningjie Sun, Jiansong Jiang, Xiansheng Chen
Cancer Cell International.2020;[Epub] CrossRef
Mismatch Repair System Genomic Scars in Gastroesophageal Cancers: Biology and Clinical Testing
Gianluca Lopez, Konstantinos Venetis, Elham Sajjadi, Nicola Fusco
Gastrointestinal Disorders.2020; 2(4): 341. CrossRef

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Soluble Axl Is a Novel Diagnostic Biomarker of Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection: Xiaoting Song, Ailu Wu, Zhixiao Ding, Shixiong Liang, Chunyan Zhang; Cancer Res Treat. 2020;52(3):789-797. Published online March 5, 2020; DOI: https://doi.org/10.4143/crt.2019.749

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate the diagnostic value of soluble Axl (sAxl) in hepatocellular carcinoma (HCC) in comparison with serum α-fetoprotein (AFP).
Materials and Methods
Eighty HCC patients, 80 liver cirrhosis patients (LC), 80 patients with hepatitis B virus (HBV) infection, and 80 healthy controls (HC) were enrolled. sAxl levels were measured by an enzyme-linked immunosorbent assay, serum AFP levelswere measured by an electrochemiluminescence immunoassay. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performances.
Results
The results show that levels of sAxl were high expression in patients with HCC (p < 0.05), varied with disease state as follows: HCC > LC > HC > HBV. Logistic regression and ROC curve analysis identified the optimal cut-off for sAxl in differentiating all HCC and non-HCC patients was 1,202 pg/mL (area under the receiver operating characteristic [AUC], 0.888; 95% confidence interval [CI], 0.852 to 0.924) with sensitivity 95.0%, specificity 73.3%. Furthermore, differential diagnosis of early HCC with non-HCC patients for sAxl showed the optimal cut-off was 1,202 pg/mL (AUC, 0.881; 95% CI, 0.831 to 0.931; sensitivity, 94.1%; specificity, 73.3%). Among AFP-negative HCC patients with non-HCC patients, the cut-off was 1,301 pg/mL (AUC, 0.898; 95% CI, 0.854 to 0.942) with a sensitivity of 84.6%, a specificity of 76.3%. The optimal cut-off for sAxl in differentiating all HCC and chronic liver disease patients was 1,243 pg/mL (AUC, 0.840; 95% CI, 0.791 to 0.888) with sensitivity 93.8%, specificity 61.9%. The combination of AFP and sAxl increased diagnostic value for HCC.
Conclusion
sAxl outperforms AFP in detecting HCC, especially in early HCC and in AFP-negative HCC. Combination sAxl with AFP improved the specificity for early HCC diagnosis. In summary, sAxl is a candidate serum marker for diagnosing HCC.

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Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review
Endrit Shahini, Giuseppe Pasculli, Antonio Giovanni Solimando, Claudio Tiribelli, Raffaele Cozzolongo, Gianluigi Giannelli
International Journal of Molecular Sciences.2023; 24(5): 4286. CrossRef
AXL in cancer: a modulator of drug resistance and therapeutic target
Yaoxiang Tang, Hongjing Zang, Qiuyuan Wen, Songqing Fan
Journal of Experimental & Clinical Cancer Research.2023;[Epub] CrossRef
Emerging biomolecules for practical theranostics of liver hepatocellular carcinoma
Miner Hu, Xiaojun Xia, Lichao Chen, Yunpeng Jin, Zhenhua Hu, Shudong Xia, Xudong Yao
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Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis
Katharina Staufer, Heidemarie Huber, Jasmin Zessner-Spitzenberg, Rudolf Stauber, Armin Finkenstedt, Heike Bantel, Thomas S. Weiss, Markus Huber, Patrick Starlinger, Thomas Gruenberger, Thomas Reiberger, Susanne Sebens, Gail McIntyre, Ray Tabibiazar, Amato
Cell Death Discovery.2023;[Epub] CrossRef
TAM Receptors in the Pathophysiology of Liver Disease
Emilio Flint, Evangelos Triantafyllou, Christine Bernsmeier
Livers.2022; 2(1): 15. CrossRef
Prognostic Value of Computed Tomography Texture Features in Patients with Hepatocellular Carcinoma Following Stereotactic Ablative Radiotherapy
Yufeng Zhu, Jie He, Xingcai Luo
Iranian Journal of Radiology.2022;[Epub] CrossRef
Abdominal ultrasound and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease
Agostino Colli, Tin Nadarevic, Damir Miletic, Vanja Giljaca, Mirella Fraquelli, Davor Štimac, Giovanni Casazza
Cochrane Database of Systematic Reviews.2021;[Epub] CrossRef
Accelerating AXL targeting for TNBC therapy
Lohit Khera, Sima Lev
The International Journal of Biochemistry & Cell Biology.2021; 139: 106057. CrossRef
Hepatocellular Carcinoma in 2021: An Exhaustive Update
Cyriac A Philips, Sasidharan Rajesh, Dinu C Nair, Rizwan Ahamed, Jinsha K Abduljaleel, Philip Augustine
Cureus.2021;[Epub] CrossRef
AXL Knock-Out in SNU475 Hepatocellular Carcinoma Cells Provides Evidence for Lethal Effect Associated with G2 Arrest and Polyploidization
Tugce Batur, Ayse Argundogan, Umur Keles, Zeynep Mutlu, Hani Alotaibi, Serif Senturk, Mehmet Ozturk
International Journal of Molecular Sciences.2021; 22(24): 13247. CrossRef
New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma
Ting Wang, Kun-He Zhang
Frontiers in Oncology.2020;[Epub] CrossRef

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BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy: Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro; Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019; DOI: https://doi.org/10.4143/crt.2018.598

Abstract PDF PubReader ePub

Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

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PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis
Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
Breast Cancer Research and Treatment.2023; 201(2): 161. CrossRef
Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
Translational Oncology.2023; 37: 101738. CrossRef
Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations
Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
JCO Precision Oncology.2022;[Epub] CrossRef
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
Ugo Testa, Germana Castelli, Elvira Pelosi
Medical Sciences.2020; 8(1): 18. CrossRef

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Dynamics of Soluble Programmed Death-Ligand 1 (sPDL1) during Chemotherapy and Its Prognostic Implications in Cancer Patients: Biomarker Development in Immuno-oncology: Hyerim Ha, Ju-Hee Bang, Ah-Rong Nam, Ji-Eun Park, Mei Hua Jin, Yung-Jue Bang, Do-Youn Oh; Cancer Res Treat. 2019;51(2):832-840. Published online October 5, 2018; DOI: https://doi.org/10.4143/crt.2018.311

Abstract PDF PubReader ePub

Purpose
The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients.
Materials and Methods
From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed.
Results
The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003).
Conclusion
The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.

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Chemotherapy driven alterations in NK cell receptors and ligands in high grade serous ovarian cancer
Pavan Kumar, Samruddhi Ranmale, Sanket Mehta, Hemant Tongaonkar, Vashishth Maniar, Jayanti Mania-Pramanik
Frontiers in Immunology.2026;[Epub] CrossRef
Electrochemical sensors for the detection of immune checkpoint related proteins and their role in cancer companion diagnostics
Louise Barnaby, Andrew G. Watts, Pedro Estrela
Biosensors and Bioelectronics: X.2025; 22: 100561. CrossRef
Soluble sFas, sFasL, sPD1, and sPDL1 Analyses in the Peripheral Blood of Locally Advanced Breast Cancer Patients Before and After Neoadjuvant Chemotherapy
Carolina de Souza Vasconcelos, Marcelo Ramos Tejo Salgado, Mario Rino Martins, Carlos Eduardo Caiado Anunciação, Denise Viana Sobral, Leuridan Cavalcante Torres
Journal of Surgical Oncology.2025; 132(5): 817. CrossRef
Identification of serum proteins associated with response of triple-negative breast cancer to neoadjuvant chemotherapy: preliminary results from the INSTIGO trial
Celeste Pinard, Angeline Ginzac, Ioana Molnar, Hugo Veyssiere, Yannick Bidet, Vincent Sapin, Julie Durif, Catherine Abrial, Frederique Penault-Llorca, Xavier Durando, Nina Radosevic-Robin
Clinical Proteomics.2025;[Epub] CrossRef
Prognostic significance of soluble PD-L1 in prostate cancer
Margarita Zvirble, Zilvinas Survila, Paulius Bosas, Neringa Dobrovolskiene, Agata Mlynska, Gintaras Zaleskis, Jurgita Jursenaite, Dainius Characiejus, Vita Pasukoniene
Frontiers in Immunology.2024;[Epub] CrossRef
Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications
Lin Chen, Yuqing Chao, Wenjing Li, Zhixia Wu, Qinchuan Wang
Biomarker Research.2024;[Epub] CrossRef
Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC
Ling Yi, Xiaojue Wang, Siyun Fu, Zhuohong Yan, Tianyu Ma, Siqi Li, Panjian Wei, Hongtao Zhang, Jinghui Wang
Discover Oncology.2023;[Epub] CrossRef
Prognostic value of soluble programmed cell death ligand-1 (sPD-L1) in lymphoma: a systematic review and meta-analysis
Yangyang Ding, Cheng Sun, Linhui Hu, Shudao Xiong, Zhimin Zhai
Annals of Hematology.2023; 102(9): 2425. CrossRef
A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
Targeted Oncology.2023; 18(6): 837. CrossRef
Does Elevated Pre-Treatment Plasma PD-L1 Level Indicate an Increased Tumor Burden and Worse Prognosis in Metastatic Colorectal Cancer?
Magdolna Dank, Dorottya Mühl, Magdolna Herold, Lilla Hornyák, Attila Marcell Szasz, Zoltan Herold
Journal of Clinical Medicine.2022; 11(16): 4815. CrossRef
The prognostic role of soluble transforming growth factor‐β and its correlation with soluble programmed death‐ligand 1 in biliary tract cancer
Jin Won Kim, Kyung‐Hun Lee, Ji‐Won Kim, Koung Jin Suh, Ah‐Rong Nam, Ju‐Hee Bang, Mei Hua Jin, Kyoung‐Seok Oh, Jae‐Min Kim, Tae‐Yong Kim, Do‐Youn Oh
Liver International.2021; 41(2): 388. CrossRef
Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients
Woochan Park, Ju-Hee Bang, Ah-Rong Nam, Mei Hua Jin, Hyerim Seo, Jae-Min Kim, Kyoung Seok Oh, Tae-Yong Kim, Do-Youn Oh
Cancer Research and Treatment.2021; 53(1): 199. CrossRef
The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas
Shujun Liu, Yadi Zhu, Chenxi Zhang, Xiangrui Meng, Bo Sun, Guojun Zhang, Yubo Fan, Xixiong Kang
Frontiers in Oncology.2020;[Epub] CrossRef
The prognostic role of soluble TGF‐beta and its dynamics in unresectable pancreatic cancer treated with chemotherapy
Hyunkyung Park, Ju‐Hee Bang, Ah‐Rong Nam, Ji Eun Park, Mei Hua Jin, Yung‐Jue Bang, Do‐Youn Oh
Cancer Medicine.2020; 9(1): 43. CrossRef
Soluble programmed death-1 (sPD-1) and programmed death ligand 1 (sPD-L1) as potential biomarkers for the diagnosis and prognosis of glioma patients
Shujun Liu, Yadi Zhu, Chenxi Zhang, Jiajia Liu, Hong Lv, Guojun Zhang, Xixiong Kang
Journal of Medical Biochemistry.2020; 39(4): 444. CrossRef
Soluble PD-1: Predictive, Prognostic, and Therapeutic Value for Cancer Immunotherapy
Muhammad Khan, Zhihong Zhao, Sumbal Arooj, Yuxiang Fu, Guixiang Liao
Frontiers in Immunology.2020;[Epub] CrossRef

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Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial: Min Hwan Kim, Xianglan Zhang, Minkyu Jung, Inkyung Jung, Hyung Soon Park, Seung-Hoon Beom, Hyo Song Kim, Sun Young Rha, Hyunki Kim, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung; Cancer Res Treat. 2019;51(2):819-831. Published online September 27, 2018; DOI: https://doi.org/10.4143/crt.2018.331

Abstract PDF Supplementary Material PubReader ePub

Purpose
Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection.
Materials and Methods
This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomy with or without adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values.
Results
Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis.
Conclusion
This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

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Checkpoint kinase 1 protein as a diagnostic marker for pleural mesothelioma
Azadeh Asghari Birbaneh, Christos Meristoudis, Caspar Bundgaard Nielsen, Weronika Maria Szejniuk, Morten Johansen, Peter Derek Christian Leutscher, Vasiliki Panou, Oluf Dimitri Røe
Journal of the American Society of Cytopathology.2026;[Epub] CrossRef
Expression of Thymidylate Synthase in Cancer: A Tissue Microarray Study Involving 17,371 Cancers from 136 Tumor Entities
Florian Lutz, Lisa Sophie Hannemann, Seyma Büyücek, Katharina Möller, Florian Viehweger, Ria Schlichter, Andreas M. Luebke, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Christian Bernreuther, Guido Sauter, David Dum, Andreas H. Marx, Ronald Simon, Til
Biomedicines.2026; 14(7): 1599. CrossRef
TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study
Hirofumi Tazawa, Shinji Hato, Shigefumi Yoshino, Shinya Otsuka, Atsusi Takeno, Kazuhiro Toyota, Hiromitsu Moriya, Isao Nozaki, Koji Tanakaya, Hideaki Uchiyama, Akihisa Saito, Kazuya Kuraoka, Takeshi Kato, Takahisa Suzuki, Hirotaka Tashiro
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Bibliometric analysis of tumor marker application in gastric cancer diagnosis from 2019 to 2024
Zhanat Komekbay, Reza Shirazi, Gulnaz Yessultanova, Alisher Garifollin, Anar Tulyayeva, Nurgul Kereyeva, Saule Akhmetova, Abdiraman Kaliev
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AI-Powered Insights into Drug Resistance in Gastric Cancer: A Path Toward Precision Therapy
Negar Mottaghi-Dastjerdi, Mohammad Soltany-Rezaee-Rad
Iranian Journal of Pharmaceutical Research.2025;[Epub] CrossRef
Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1–Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial
Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung
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Utility of TMPRSS4 as a Prognostic Biomarker and Potential Therapeutic Target in Patients with Gastric Cancer
Hirofumi Tazawa, Takahisa Suzuki, Akihisa Saito, Akira Ishikawa, Toshiaki Komo, Haruki Sada, Norimitsu Shimada, Naoto Hadano, Takashi Onoe, Takeshi Sudo, Yosuke Shimizu, Kazuya Kuraoka, Hirotaka Tashiro
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Scoring systems for PD-L1 expression and their prognostic impact in patients with resectable gastric cancer
Marina Alessandra Pereira, Marcus Fernando Kodama Pertille Ramos, André Roncon Dias, Renan Ribeiro, Leonardo Cardili, Bruno Zilberstein, Ivan Cecconello, Ulysses Ribeiro, Evandro Sobroza de Mello, Tiago Biachi de Castria
Virchows Archiv.2021; 478(6): 1039. CrossRef
Epstein–Barr Virus Positive Gastric Cancer: A Distinct Subtype Candidate for Immunotherapy
Marina Alessandra Pereira, Daniel Amadeus Molon Batista, Marcus Fernando Kodama Pertille Ramos, Leonardo Cardili, Renan Ribeiro e Ribeiro, Andre Roncon Dias, Bruno Zilberstein, Ulysses Ribeiro Jr, Ivan Cecconello, Venâncio Avancini Ferreira Alves, Evandro
Journal of Surgical Research.2021; 261: 130. CrossRef
Cytotoxic T‐lymphocyte‐associated protein 4 in gastric cancer: Prognosis and association with PD‐L1 expression
Marina Alessandra Pereira, Tiago Biachi de Castria, Marcus Fernando Kodama Pertille Ramos, André Roncon Dias, Leonardo Cardili, Rafael Dyer Rodrigues de Moraes, Bruno Zilberstein, Sergio Carlos Nahas, Ulysses Ribeiro, Evandro Sobroza de Mello
Journal of Surgical Oncology.2021; 124(7): 1040. CrossRef
Remnant gastric cancer: a neglected group with high potential for immunotherapy
Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, Tiago Biachi de Castria, Renan Ribeiro e Ribeiro, Leonardo Cardili, Evandro Sobroza de Mello, Bruno Zilberstein, Ulysses Ribeiro-Júnior, Ivan Cecconello
Journal of Cancer Research and Clinical Oncology.2020; 146(12): 3373. CrossRef
Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma
Jose J. G. Marin, Laura Perez-Silva, Rocio I. R. Macias, Maitane Asensio, Ana Peleteiro-Vigil, Anabel Sanchez-Martin, Candela Cives-Losada, Paula Sanchon-Sanchez, Beatriz Sanchez De Blas, Elisa Herraez, Oscar Briz, Elisa Lozano
Cancers.2020; 12(8): 2116. CrossRef
Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer
Seo Ree Kim, Kabsoo Shin, Jae Myung Park, Han Hong Lee, Kyo Yong Song, Sung Hak Lee, Bohyun Kim, Sang-Yeob Kim, Junyoung Seo, Jeong-Oh Kim, Sang-Young Roh, In-Ho Kim
Journal of Gastric Cancer.2020; 20(4): 408. CrossRef
Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
van den Ende, ter Veer, Mali, van Berge Henegouwen, Hulshof, van Oijen, van Laarhoven
Cancers.2019; 11(4): 530. CrossRef

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Plasma Macrophage Migration Inhibitory Factor and CCL3 as Potential Biomarkers for Distinguishing Patients with Nasopharyngeal Carcinoma from High-Risk Individuals Who Have Positive Epstein-Barr Virus Capsid Antigen-Specific IgA: Ning Xue, Jian-Hua Lin, Shan Xing, Dan Liu, Shi-Bing Li, Yan-Zhen Lai, Xue-Ping Wang, Min-Jie Mao, Qian Zhong, Mu-Sheng Zeng, Wan-Li Liu; Cancer Res Treat. 2019;51(1):378-390. Published online May 29, 2018; DOI: https://doi.org/10.4143/crt.2018.070

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA).
Materials and Methods
One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques.
Results
Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues.
Conclusion
Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.

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Serum Chemokines CCL3 and CCL7 as Complementary Diagnostic Biomarkers Across Tumor Grades in Clear Cell Renal Cell Carcinoma
Weronika Sokólska, Monika Zajkowska, Agnieszka Kulczyńska-Przybik, Tadeusz Werel, Karolina Orywal
International Journal of Molecular Sciences.2026; 27(5): 2490. CrossRef
Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis
Vikrant Kumar, Nawaid Hussain Khan, Shashi Nandar Kumar, Neeraj Mahajan, Wafa Aziz, Vinay Kumar, Chaitenya Verma, Harleen Khatra
Biochemistry Research International.2026;[Epub] CrossRef
Roles of Macrophage Migration Inhibitory Factor (MIF) Signaling Pathway in Oncovirus Infection and Virus-Associated Cancers
Jiaojiao Fan, Victor Ryu, Zhiqiang Qin, Lu Dai
Viruses.2025; 17(12): 1582. CrossRef
Nasopharyngeal carcinoma-associated inflammatory cytokines: ongoing biomarkers
Chuwen Liang, Jun Kan, Jingli Wang, Wei Lu, Xiaoyan Mo, Bei Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Genetic Variants of the MIF Gene and Susceptibility of Rectal Cancer
Dongyu Chuo, Dapeng Lin, Mingdi Yin, Yuze Chen
Pharmacogenomics and Personalized Medicine.2021; Volume 14: 55. CrossRef
microRNA-451 (miR-451) Regulates the Apoptosis of Non-Small Cell Lung Cancer Cells by Targeting Macrophage Migration Promoting Factors
Caihong Wei, Dan Guo, Huayun Pu
Journal of Biomaterials and Tissue Engineering.2021; 11(7): 1388. CrossRef

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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma: Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim; Cancer Res Treat. 2019;51(1):300-312. Published online May 9, 2018; DOI: https://doi.org/10.4143/crt.2018.012

Abstract PDF Supplementary Material PubReader ePub

Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

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Exploratory Biomarker Analysis of Abemaciclib in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma With Dysregulated CDK4/6 Pathway
Joo‐Hwan Park, Hee Kyung Ahn, Hye Ryun Kim, Soyeon Kim, Keon‐Uk Park, Tak Yun, Hyo Jung Kim, Sang‐Cheol Lee, Sang Hee Cho, Sang‐Gon Park, Bhumsuk Keam, Hwan Jung Yun
Head & Neck.2026; 48(6): 1547. CrossRef
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Angeliki Margoni, Kostas A. Papavassiliou, Athanasios G. Papavassiliou
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Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer: Soomin Ahn, Hyun Jeong Kim, Milim Kim, Yul Ri Chung, Eunyoung Kang, Eun-Kyu Kim, Se Hyun Kim, Yu Jung Kim, Jee Hyun Kim, In Ah Kim, So Yeon Park; Cancer Res Treat. 2018;50(4):1418-1432. Published online January 24, 2018; DOI: https://doi.org/10.4143/crt.2017.552

Abstract PDF PubReader ePub

Purpose
Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST.
Materials and Methods
The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed.
Results
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup.
Conclusion
ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

Citations

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Ki‐67 Dynamics and Biomarker Conversion as Prognostic Factors in Residual Breast Cancer
Ömer Faruk Elçiçek, Eyyüp Çavdar, Özge Yalıcı, Ezel Gedik, Meltem Öznur, Yıldız Garip Bilen, İlker Karaduman, Okan Avcı, Erdoğan Selçuk Şeber
Asia-Pacific Journal of Clinical Oncology.2026;[Epub] CrossRef
Impact of hormone receptor and HER2 conversions on survival after neoadjuvant chemotherapy in breast cancer patients
Ran Feng, Lihui Pan, Yarong Yao, Jinnan Gao, Xiaojun Zhang
Oncology and Translational Medicine.2025; 11(2): 73. CrossRef
Epigenetic therapeutics: reprogramming triple-negative breast cancer into responsive subtypes
Wafaa S Ramadan, Aya Mudhafar Al-Azawi, Lama Lozon, Rawan R Kawaf, Ragheb Alsheikh Zein, Yahia El-Gharib, Raafat El-Awady
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Changing the phenotype of breast cancer in the process treatment: literature review
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Xia Wang, Dechun Xing, Zheng Liu, Yujing Zhang, Bo Cheng, Suozhu Sun, Qingtao Wang, Lianhua Dong
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Yang He, Jing Zhang, Hui Chen, Ying Zhou, Liping Hong, Yue Ma, Nannan Chen, Weipeng Zhao, Zhongsheng Tong
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Jiaqi Bo, Baohua Yu, Rui Bi, Xiaoli Xu, Yufan Cheng, Xiaoyu Tu, Qianming Bai, Wentao Yang, Ruohong Shui
Clinical Breast Cancer.2023; 23(4): 436. CrossRef
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Imane Eliahiai, Mohammed Eljiar, Sanae Chaib, Jinane KHarmoum, Mariame Chraïbi
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Luo Wang, Qi Jiang, Meng-Ye He, Peng Shen
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L. V. Bolotina, A. L. Kornietskaya, A. A. Kachmazov, N. S. Prizova, A. A. Paichadze, T. V. Ustinova, T. I. Deshkina, S. F. Evdokimova
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Hai-Qing Liu, Si-Ying Lin, Yi-Dong Song, Si-Yao Mai, Yue-dong Yang, Kai Chen, Zhuo Wu, Hui-Ying Zhao
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Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer
Mengping Long, Chong You, Qianqian Song, Lina Hu, Zhaorong Guo, Qian Yao, Wei Hou, Wei Sun, Baosheng Liang, Xiao-Hua Zhou, Yiqiang Liu, Taobo Hu
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The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer
M G Davey, É J Ryan, P J Folan, N O’Halloran, M R Boland, M K Barry, K J Sweeney, C M Malone, R J McLaughlin, M J Kerin, A J Lowery
BJS Open.2021;[Epub] CrossRef
Prognostic implications of regression of metastatic axillary lymph nodes after neoadjuvant chemotherapy in patients with breast cancer
Yul Ri Chung, Ji Won Woo, Soomin Ahn, Eunyoung Kang, Eun-Kyu Kim, Mijung Jang, Sun Mi Kim, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
Scientific Reports.2021;[Epub] CrossRef
Enriched transcriptome analysis of laser capture microdissected populations of single cells to investigate intracellular heterogeneity in immunostained FFPE sections
Sarah M. Hammoudeh, Arabella M. Hammoudeh, Thenmozhi Venkatachalam, Surendra Rawat, Manju N. Jayakumar, Mohamed Rahmani, Rifat Hamoudi
Computational and Structural Biotechnology Journal.2021; 19: 5198. CrossRef
Lost but Not Least—Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer
Michał Kunc, Marta Popęda, Wojciech Biernat, Elżbieta Senkus
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Biomarkers Changes after Neoadjuvant Chemotherapy in Breast Cancer: A Seven-Year Single Institution Experience
Saverio Coiro, Elisa Gasparini, Giuseppe Falco, Giacomo Santandrea, Moira Foroni, Giulia Besutti, Valentina Iotti, Roberto Di Cicilia, Monica Foroni, Simone Mele, Guglielmo Ferrari, Giancarlo Bisagni, Moira Ragazzi
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HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation
Soomin Ahn, Ji Won Woo, Kyoungyul Lee, So Yeon Park
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Effect of neoadjuvant therapy on breast cancer biomarker profile
Laura Rey-Vargas, Juan Carlos Mejía-Henao, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez
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Changes in Biomarker Status in Metastatic Breast Cancer and Their Prognostic Value
Ji Won Woo, Yul Ri Chung, Soomin Ahn, Eunyoung Kang, Eun-Kyu Kim, Se Hyun Kim, Jee Hyun Kim, In Ah Kim, So Yeon Park
Journal of Breast Cancer.2019; 22(3): 439. CrossRef

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Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05): Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park; Cancer Res Treat. 2018;50(4):1252-1259. Published online January 2, 2018; DOI: https://doi.org/10.4143/crt.2017.438

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).
Materials and Methods
This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed.
Results
Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
Conclusion
Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.

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Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma: Eun-Jung Lee, Seung-Hyun Yang, Kyoung-Jin Kim, Hyejung Cha, Seo Jin Lee, Ji-Hye Kim, Junkyu Song, Kyung-Hee Chun, Jinsil Seong; Cancer Res Treat. 2018;50(3):646-657. Published online July 17, 2017; DOI: https://doi.org/10.4143/crt.2016.550

Abstract PDF Supplementary Material PubReader ePub

Purpose
Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins.
Materials and Methods
2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells.
Results
Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis.
Conclusion
Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.

Citations

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