Cancer Research and Treatment

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; Received December 18, 2024 Accepted January 22, 2025 Published online January 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1222 [Accepted]

Abstract PDF: 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.

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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.

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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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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.

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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.

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Minimal residual disease as a target for liquid biopsy in patients with solid tumours
Klaus Pantel, Catherine Alix-Panabières
Nature Reviews Clinical Oncology.2025; 22(1): 65. CrossRef
Role of Liquid Biopsy in Progressive PSA Patients after Radical Prostatectomy
Marcel Figueras, Lourdes Mengual, Mercedes Ingelmo-Torres, Fiorella L. Roldán, Bernat Padullés, Héctor Alfambra, Sandra Herranz, Pilar Paredes, Gary Amseian, Joel Mases, Maria J. Ribal, Laura Izquierdo, Antonio Alcaraz
Diagnostics.2024; 14(20): 2293. CrossRef
Circulating Tumor DNA Is a Variant of Liquid Biopsy with Predictive and Prognostic Clinical Value in Breast Cancer Patients
Tatiana M. Zavarykina, Polina K. Lomskova, Irina V. Pronina, Svetlana V. Khokhlova, Marina B. Stenina, Gennady T. Sukhikh
International Journal of Molecular Sciences.2023; 24(23): 17073. CrossRef

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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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Clinical use of circulating tumor DNA analysis in patients with lymphoma
Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
Human Pathology.2025; 156: 105679. CrossRef
Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
Molecular Cancer.2024;[Epub] CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Minimal residual disease detection in lymphoma: methods, procedures and clinical significance
Sijun Zhang, Xiangyu Wang, Zhenzhen Yang, Mengjie Ding, Mingzhi Zhang, Ken H. Young, Xudong Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas
Laurence de Leval, Philippe Gaulard, Ahmet Dogan
Blood.2024; 144(18): 1855. CrossRef
In-depth circulating tumor DNA sequencing for prognostication and monitoring in natural killer/T-cell lymphomas
Jin Ju Kim, Hyun-Young Kim, Zisun Choi, So yoon Hwang, Hansol Jeong, Jong Rak Choi, Sang Eun Yoon, Won Seog Kim, Sun-Hee Kim, Hee-Jin Kim, Sang-Yong Shin, Seung-Tae Lee, Seok Jin Kim
Frontiers in Oncology.2023;[Epub] CrossRef
Circulating tumor DNA in NK/T and peripheral T cell lymphoma
Yu-Jia Huo, Wei-Li Zhao
Seminars in Hematology.2023; 60(3): 173. CrossRef
A genetic profiling guideline to support diagnosis and clinical management of lymphomas
Margarita Sánchez-Beato, Miriam Méndez, María Guirado, Lucía Pedrosa, Silvia Sequero, Natalia Yanguas-Casás, Luis de la Cruz-Merino, Laura Gálvez, Marta Llanos, Juan Fernando García, Mariano Provencio
Clinical and Translational Oncology.2023; 26(5): 1043. CrossRef

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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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The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
Yasemin Cakir, Banu Lebe
Applied Immunohistochemistry & Molecular Morphology.2025; 33(2): 117. CrossRef
Exploration of the regulatory mechanism of norcantharidin on sine oculis homeobox homolog 4 in colon cancer using transcriptome sequencing and bioinformatic
Fanqin Zhang, Chao Wu, Jingyuan Zhang, Zhihong Huang, Antony Stalin, Yiyan Zhai, Shuqi Liu, Jiarui Wu
Journal of Traditional Chinese Medical Sciences.2025;[Epub] CrossRef
Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef
An Insight into the Peculiarities of Signet-Ring Cell Carcinoma of the Colon – a Narrative Review
Loredana Farcaș, Diana Voskuil-Galoș
Journal of Medical and Radiation Oncology.2024; 4(7): 1. CrossRef
High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
Hannah Yang, Beodeul Kang, Yeonjung Ha, Sung Hwan Lee, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Gwangil Kim, Sanghoon Jung, Sun Young Rha, Vincent E. Gaillard, Jaekyung Cheon, Chan Kim, Hong Jae Chon
JHEP Reports.2023; 5(4): 100672. CrossRef
Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer
Zhe Yang, Feiran Chen, Feng Wang, Xiubing Chen, Biaolin Zheng, Xiaomin Liao, Zhejun Deng, Xianxian Ruan, Jing Ning, Qing Li, Haixing Jiang, Shanyu Qin
BMC Cancer.2023;[Epub] CrossRef
PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
Heyam A. Awad, Maher A. Sughayer, Jumana M. Obeid, Yaqoot N. Heilat, Ahmad S. Alhesa, Reda M. Yousef, Nabil M. Hasasna, Shafiq A. Masoud, Tareq Saleh
Applied Immunohistochemistry & Molecular Morphology.2023; 31(6): 379. CrossRef
Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
Small.2023;[Epub] CrossRef
Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment
Norah A. Alturki
Journal of Clinical Medicine.2023; 12(13): 4301. CrossRef
Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives
Nian-Nian Zhong, Han-Qi Wang, Xin-Yue Huang, Zi-Zhan Li, Lei-Ming Cao, Fang-Yi Huo, Bing Liu, Lin-Lin Bu
Seminars in Cancer Biology.2023; 95: 52. CrossRef
Artificial intelligence for prediction of response to cancer immunotherapy
Yuhan Yang, Yunuo Zhao, Xici Liu, Juan Huang
Seminars in Cancer Biology.2022; 87: 137. CrossRef

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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.

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A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes
Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri
eLife.2024;[Epub] CrossRef
A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes
Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri
eLife.2024;[Epub] CrossRef
Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer
Qi Chang, Yongqiang Chen, Jianjian Yin, Tao Wang, Yuanheng Dai, Zixin Wu, Yufeng Guo, Lingang Wang, Yufen Zhao, Hang Yuan, Dongkui Song, Lirong Zhang
Journal of Proteome Research.2024; 23(6): 2241. CrossRef
Construction of noninvasive prognostic model of bladder cancer patients based on urine proteomics and screening of natural compounds
Shun Wan, Jinlong Cao, Siyu Chen, Jianwei Yang, Huabin Wang, Chenyang Wang, Kunpeng Li, Li Yang
Journal of Cancer Research and Clinical Oncology.2023; 149(1): 281. CrossRef
Extracellular Vesicles as Potential Bladder Cancer Biomarkers: Take It or Leave It?
Ana Teixeira-Marques, Catarina Lourenço, Miguel Carlos Oliveira, Rui Henrique, Carmen Jerónimo
International Journal of Molecular Sciences.2023; 24(7): 6757. CrossRef
Advances in the application of label‐free quantitative proteomics techniques in malignancy research
Xiao Meng, Dong Liu, Yan Guan
Biomedical Chromatography.2023;[Epub] CrossRef
Off the fog to find the optimal choice: Research advances in biomarkers for early diagnosis and recurrence monitoring of bladder cancer
Jiaxin Zhao, Jinming Li, Rui Zhang
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2023; 1878(4): 188926. CrossRef
An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value
Henrique Caracho Ribeiro, Flávia da Silva Zandonadi, Alessandra Sussulini
Expert Review of Proteomics.2023; 20(11): 267. CrossRef
Proteome and immune responses of extracellular vesicles derived from macrophages infected with the periodontal pathogen Tannerella forsythia
Younggap Lim, Hyun Young Kim, Dohyun Han, Bong‐Kyu Choi
Journal of Extracellular Vesicles.2023;[Epub] CrossRef
A Liquid Biopsy in Bladder Cancer—The Current Landscape in Urinary Biomarkers
Milena Matuszczak, Adam Kiljańczyk, Maciej Salagierski
International Journal of Molecular Sciences.2022; 23(15): 8597. CrossRef
Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19
Takahiro Kawasaki, Yoshito Takeda, Ryuya Edahiro, Yuya Shirai, Mari Nogami-Itoh, Takanori Matsuki, Hiroshi Kida, Takatoshi Enomoto, Reina Hara, Yoshimi Noda, Yuichi Adachi, Takayuki Niitsu, Saori Amiya, Yuta Yamaguchi, Teruaki Murakami, Yasuhiro Kato, Tak
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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.

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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.

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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
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Head & Neck.2025;[Epub] CrossRef
Exploring Surgical Oncology-Based Comparative and Systematic Analysis of the Diagnostic Potential of Various Novel Biomarkers in Head and Neck Squamous Cell Carcinoma
Mostafa Ahmed Abdellah Ahmed, Amna Batool, Aws Khaled Mohammad Rababah, Madeeha Minhas, Abdul Mannan Jehangir, Maryum Sana, Muhammad Haseeb, Ehsan Ul Haq Mzahri
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Lei Liu, Qiang Liu
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Quan Wang, Xiangzhi Yin, Shengxia Wang, Haijun Lu
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Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma
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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Tibera K. Rugambwa, Omar Abdihamid, Xiangyang Zhang, Yinghui Peng, Changjing Cai, Hong Shen, Shan Zeng, Wei Qiu
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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
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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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Xing-xing Huo, Shu-jie Wang, Hang Song, Ming-de Li, Hua Yu, Meng Wang, Hong-xiao Gong, Xiao-ting Qiu, Yong-fu Zhu, Jian-ye Zhang
Frontiers in Pharmacology.2021;[Epub] CrossRef

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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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Junchen Guo, Liang Zhao, Meiqi Duan, Zhi Yang, He Zhao, Baiming Liu, Yihan Wang, Liping Deng, Chen Wang, Xiaodi Jiang, Xiaofeng Jiang
Biomedicine & Pharmacotherapy.2024; 174: 116479. CrossRef
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Liushan Wei, Shun Liu, Zhizhong Xie, Guotao Tang, Xiaoyong Lei, Xiaoyan Yang
International Immunopharmacology.2024; 140: 112824. CrossRef
Simultaneous detection of membrane protein and mRNA at single extracellular vesicle level by droplet microfluidics for cancer diagnosis
Huixian Lin, Bo Li, Jingyun Guo, Xueying Mai, Haiyang Yu, Weilun Pan, Bodeng Wu, Wei Liu, Mingzhen Zhong, Tong Liao, Ye Zhang, Bo Situ, Xiaohui Yan, Yifan Liu, Chunchen Liu, Lei Zheng
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Huhu Zhang, Fulin Sun, Shuyao Jiang, Fanghao Yang, Xiaolei Dong, Guoxiang Liu, Mengjun Wang, Ya Li, Mohan Su, Ziyuan Wen, Chunjuan Yu, Chenkai Fan, Xiaoxia Li, Zhe Zhang, Lina Yang, Bing Li
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Yinghao Fang, Yuyan Xu, Wei Liao, Tao Ji, Linyuan Yu, Longhai Li, Mingxin Pan, Dinghua Yang
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Martyna Jastrzębska, Joanna Giebułtowicz, Andrzej K. Ciechanowicz, Robert Wrzesień, Wojciech Bielecki, Barbara Bobrowska-Korczak
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Xiaolin Qu, Yongqiu Zhang, Xianzheng Sang, Ding Ren, Hong Zhao, Stephen T. C. Wong
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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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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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Esra KEKİLLİ, Ebru ATASEVER AKKAŞ, Serab UYAR, Emre YEKEDÜZ
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Yalan Yang, Dao Xin, Huike Wang, Lulu Guan, Xiangrui Meng, Taiying Lu, Xiwen Bai, Feng 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,
World Journal of Gastroenterology.2022; 28(21): 2302. CrossRef
Pathologic Complete Response Prediction to Neoadjuvant Immunotherapy Combined with Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: Real-World Evidence from Integrative Inflammatory and Nutritional Scores
Jifeng Feng, Liang Wang, Xun Yang, Qixun Chen, Xiangdong Cheng
Journal of Inflammation Research.2022; Volume 15: 3783. CrossRef
The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Pathological Response for Resectable Non–Small Cell Lung Cancer Treated with Neoadjuvant Chemotherapy Combined with PD-1 Checkpoint Inhibitors
Xiaoyan Sun, Yingnan Feng, Bin Zhang, Wuhao Huang, Xiaoliang Zhao, Hua Zhang, Dongsheng Yue, Changli Wang
Cancer Research and Treatment.2022; 54(4): 1017. CrossRef
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
Frontiers in Immunology.2022;[Epub] CrossRef

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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.

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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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5 Crossref

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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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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Pooja Basthi Mohan, Rajiv Lochan, Shiran Shetty
Indian Journal of Surgical Oncology.2024; 15(S2): 261. CrossRef
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Daria Apostolo, Luciana L. Ferreira, Federica Vincenzi, Nicole Vercellino, Rosalba Minisini, Federico Latini, Barbara Ferrari, Michela E. Burlone, Mario Pirisi, Mattia Bellan
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Anna Tutusaus, Albert Morales, Pablo García de Frutos, Montserrat Marí
Seminars in Liver Disease.2024; 44(01): 099. CrossRef
Dynamic changes in immune cell populations by AXL kinase targeting diminish liver inflammation and fibrosis in experimental MASH
Sturla Magnus Grøndal, Anna Tutusaus, Loreto Boix, Maria Reig, Magnus Blø, Linn Hodneland, Gro Gausdal, Akil Jackson, Pablo Garcia de Frutos, James Bradley Lorens, Albert Morales, Montserrat Marí
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Evaluating soluble Axl as a biomarker for glioblastoma: A pilot study
Daniel Raymond, Melanie Fukui, Samuel Zwernik, Amin Kassam, Richard Rovin, Parvez Akhtar, Salvatore V. Pizzo
PLOS ONE.2024; 19(7): e0301739. CrossRef
A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma
Bing-yao Pang, Yan Leng, Xiaoli Wang, Yi-qiang Wang, Li-hong Jiang
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Endrit Shahini, Giuseppe Pasculli, Antonio Giovanni Solimando, Claudio Tiribelli, Raffaele Cozzolongo, Gianluigi Giannelli
International Journal of Molecular Sciences.2023; 24(5): 4286. CrossRef
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Yaoxiang Tang, Hongjing Zang, Qiuyuan Wen, Songqing Fan
Journal of Experimental & Clinical Cancer Research.2023;[Epub] CrossRef
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Miner Hu, Xiaojun Xia, Lichao Chen, Yunpeng Jin, Zhenhua Hu, Shudong Xia, Xudong Yao
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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
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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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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
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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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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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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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
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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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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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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.

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Laura Rey-Vargas, Juan Carlos Mejía-Henao, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez
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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.

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Yingying Sun, Jie Jin, Hongyan Jing, Yingying Lu, Qingqing Zhu, Changjuan Shu, Qinghua Zhang, Dadao Jing
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Disease Markers.2019; 2019: 1. CrossRef

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Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy: Lingyun Liu, Wei Wang, Yi Zhang, Jianting Long, Zhaohui Zhang, Qiao Li, Bin Chen, Shaoqiang Li, Yunpeng Hua, Shunli Shen, Baogang Peng; Cancer Res Treat. 2018;50(2):538-550. Published online June 1, 2017; DOI: https://doi.org/10.4143/crt.2017.106

Abstract PDF PubReader ePub

Purpose
Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection.
Materials and Methods
Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses.
Results
The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients.
Conclusion
Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.

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Guo-Le Nie, Jun Yan, Ying Li, Hong-Long Zhang, Dan-Na Xie, Xing-Wang Zhu, Xun Li
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琪栋陈
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The preoperative scoring system combining neutrophil/lymphocyte ratio and CA19-9 predicts the long-term prognosis of intrahepatic cholangiocarcinoma patients undergoing curative liver resection
Shilei Bai, Xiaodong Shi, Yizhe Dai, Huifeng Wang, Yong Xia, Jian Liu, Kui Wang
BMC Cancer.2024;[Epub] CrossRef
Multifaceted roles of neutrophils in tumor microenvironment
Xueyin Pan, Qiang Wang, Beicheng Sun
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Jinming Fu, Fenqi Du, Tian Tian, Hao Huang, Lei Zhang, Dapeng Li, Yupeng Liu, Ding Zhang, Lijing Gao, Ting Zheng, Yanlong Liu, Yashuang Zhao
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Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes
Zimin Song, Shuirong Lin, Xiwen Wu, Xiaoxue Ren, Yifan Wu, Haoxiang Wen, Baifeng Qian, Haozhong Lin, Yihao Huang, Chenfeng Zhao, Nian Wang, Yan Huang, Baogang Peng, Xiaoxing Li, Hong Peng, Shunli Shen
Hepatology International.2023; 17(5): 1300. CrossRef
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Shuirong Lin, Zimin Song, Hong Peng, Baifeng Qian, Haozhong Lin, Xiwen Wu, Huilong Li, Yunpeng Hua, Baogang Peng, Changzhen Shang, Ming Kuang, Shunli Shen
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Kai Wang, Qidi Zhao, Tao Yan, Deyu Guo, Jichang Liu, Guanghui Wang, Jiajun Du
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Hui Li, Rongqiang Liu, Jiawang Li, Jiaxin Li, Hong Wu, Genshu Wang, Zhenhua Li, Dewei Li
Journal of Cellular and Molecular Medicine.2022; 26(11): 3196. CrossRef
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Qichen Chen, Mingxia Li, Jinghua Chen, Zhen Huang, Xiao Chen, Hong Zhao, Jianqiang Cai
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Zehao Zheng, Renguo Guan, Yiping Zou, Zhixiang Jian, Ye Lin, Rongping Guo, Haosheng Jin
Journal of Inflammation Research.2022; Volume 15: 5089. CrossRef
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Saygın ALTINER, Enes CEBECİ, Bedri Burak SUCU, Mert ÇÖL, Ender ERGÜDER, Yılmaz ÜNAL, Salih TUNCAL, Mevlüt Recep PEKCİCİ
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Abdullah DURHAN, Abdullah ŞENLİKCİ, Ender ERGÜDER, Marlen SÜLEYMAN, Koray KOŞMAZ, Ümit MERCAN, Mevlüt Recep PEKCİCİ, Serap EREL
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Junjie Kong, Shu Shen, Zifei Zhang, Wentao Wang
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High C-reactive protein/albumin ratio associated with reduced survival due to advanced stage of intrahepatic cholangiocarcinoma
Hisao Kano, Yutaka Midorikawa, Peipei Song, Hisashi Nakayama, Masamichi Moriguchi, Tokio Higaki, Shingo Tsuji, Tadatoshi Takayama
BioScience Trends.2020; 14(4): 304. CrossRef
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Fengming Ji, Qiang Kang, Lianmin Wang, Lixin Liu, Yang Ke, Ya Zhu, Naiqiang Zhang, Shifeng Xiong, Yuehua Li, Hao Zou
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Charupong Saengboonmee, Kanlayanee Sawanyawisuth, Yaovalux Chamgramol, Sopit Wongkham
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Lingyun Liu, Jian Wu, Yu Guo, Wenxuan Xie, Bin Chen, Yi Zhang, Shaoqiang Li, Yunpeng Hua, Baogang Peng, Shunli Shen
Aging.2018; 10(12): 4120. CrossRef

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CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy: Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2017;49(3):807-815. Published online January 18, 2017; DOI: https://doi.org/10.4143/crt.2016.326

Abstract PDF PubReader ePub

Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

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Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
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Meta-Analysis

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis: Chiara Cremolini, Carlotta Antoniotti, Filippo Pietrantonio, Rosa Berenato, Marco Tampellini, Chiara Baratelli, Lisa Salvatore, Federica Marmorino, Beatrice Borelli, Federico Nichetti, Paolo Bironzo, Cristina Sonetto, Maria Di Bartolomeo, Filippo de Braud, Fotios Loupakis, Alfredo Falcone, Massimo Di Maio; Cancer Res Treat. 2017;49(3):834-845. Published online November 15, 2016; DOI: https://doi.org/10.4143/crt.2016.249

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).
Materials and Methods
A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson’s correlation coefficient (R) and the coefficient of determination (R²).
Results
Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R²=0.539, p < 0.001) and poor correlation (R=0.169, R²=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident.
Conclusion
Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

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Original Articles

FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition: Sang Hee Cho, Chang Soo Hong, Hee Nam Kim, Min Ho Shin, Ka Rham Kim, Hyun Jeong Shim, Jun Eul Hwang, Woo Kyun Bae, Ik Joo Chung; Cancer Res Treat. 2017;49(3):766-777. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.457

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patientswith resected colon cancer, including the underlying mechanism.
Materials and Methods
FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.
Results
Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.
Conclusion
The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

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Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment
Alessandro Ottaiano, Mariachiara Santorsola, Monica Ianniello, Anna Ceccarelli, Marika Casillo, Francesco Sabbatino, Nadia Petrillo, Marco Cascella, Francesco Caraglia, Carmine Picone, Francesco Perri, Roberto Sirica, Silvia Zappavigna, Guglielmo Nasti, G
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Comprehensive analysis of the prognostic value and immune infiltration of FGFR family members in gastric cancer
Chengcheng Yang, Dingli Song, Fengyu Zhao, Jie Wu, Boxiang Zhang, Hong Ren, Qi Sun, Sida Qin
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Inhibition of FGF‐FGFR and VEGF‐VEGFR signalling in cancer treatment
Guihong Liu, Tao Chen, Zhenyu Ding, Yang Wang, Yuquan Wei, Xiawei Wei
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Every breath you take: Impacts of environmental dust exposure on intestinal barrier function–from the gut-lung axis to COVID-19
Meli’sa S. Crawford, Tara M. Nordgren, Declan F. McCole
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(4): G586. CrossRef
FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
Jung Han Kim, Soo Young Jeong, Hyun Joo Jang, Sung Taek Park, Hyeong Su Kim
Frontiers in Oncology.2021;[Epub] CrossRef
FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
Cancers.2021; 13(22): 5796. CrossRef
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Chang‐Soo Hong, Eun‐Gene Sun, Ji‐Na Choi, Dae‐Hwan Kim, Jo‐Heon Kim, Kyung‐Hyun Ryu, Hyun‐Jeong Shim, Jun‐Eul Hwang, Woo‐Kyun Bae, Hyeong‐Rok Kim, Kyung Keun Kim, Chaeyong Jung, Ik‐Joo Chung, Sang‐Hee Cho
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Blocking Interleukin-4 Receptor α Using Polyethylene Glycol Functionalized Superparamagnetic Iron Oxide Nanocarriers to Inhibit Breast Cancer Cell Proliferation: Abjal Pasha Shaik, Asma Sultana Shaik, Ali Al Majwal, Achraf Al Faraj; Cancer Res Treat. 2017;49(2):322-329. Published online July 12, 2016; DOI: https://doi.org/10.4143/crt.2016.091

Abstract PDF PubReader ePub

Purpose
The specific targeting of interleukin-4 receptor α (IL4Rα) receptor offers a promising therapeutic approach for inhibition of tumor cell progression in breast cancer patients. In the current study, the in vitro efficacy of superparamagnetic iron oxide nanoparticles conjugated with anti-IL4Rα blocking antibodies (SPION-IL4Rα) via polyethylene glycol polymers was evaluated in 4T1 breast cancer cells.
Materials and Methods
Cell viability, reactive oxygen species generation, and apoptosis frequency were assessed in vitro in 4T1 cancer cell lines following exposure to SPION-IL4Rα alone or combined with doxorubicin. In addition, immunofluorescence assessments and fluorimetrywere performed to confirm the specific targeting and interaction of the developed nanocarriers with IL4Rα receptors in breast cancer cells.
Results
Blocking of IL4Rα receptors caused a significant decrease in cell viability and induced apoptosis in 4T1 cells. In addition, combined treatment with SPION-IL4Rα+doxorubicin caused significant increases in cell death, apoptosis, and oxidative stress compared to either SPION-IL4Rα or doxorubicin alone, indicating the enhanced therapeutic efficacy of this combination. The decrease in fluorescence intensity upon immunofluorescence and fluorimetry assays combined with increased viability and decreased apoptosis following the blocking of IL4Rα receptors confirmed the successful binding of the synthesized nanocarriers to the target sites on murine 4T1 breast cancerous cells.
Conclusion
These results suggest that SPION-IL4Rα nanocarriers might be used for successfulreduction of tumor growth and inhibition of progression of metastasis in vivo.

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Sruthi Laakshmi Mugundhan, Mothilal Mohan
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Jaishree S., Kousalya Selvaraj, Prakash S., Vineesh D.
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Naseem Akhtar, Hamdoon A. Mohammed, Mohammed Yusuf, Amal Al-Subaiyel, Ghassan M. Sulaiman, Riaz A. Khan
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Veronica Manescu (Paltanea), Gheorghe Paltanea, Iulian Antoniac, Marius Vasilescu
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Mahboubeh Nabavinia, Juan Beltran-Huarac
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Mi-Ae Kang, Jongsung Lee, Sang Ha, Chang Lee, Kyoung Kim, Kyu Jang, See-Hyoung Park
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Cari L. Meisel, Polly Bainbridge, Dimitrios Mitsouras, Joyce Y. Wong
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Adil M. Allahverdiyev, Etkin Parlar, Sahar Dinparvar, Melahat Bagirova, Emrah Şefik Abamor
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Jörgen Elgqvist
International Journal of Molecular Sciences.2017; 18(5): 1102. CrossRef

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Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy: Seung Hyeun Lee, Sue In Choi, Ji Sung Lee, Chul Hwan Kim, Won Jai Jung, Eun Joo Lee, Kyung Hoon Min, Gyu Young Hur, Seung Heon Lee, Sung Yong Lee, Je Hyeong Kim, Sang Yeub Lee, Chol Shin, Jae Jeong Shim, Kyung Ho Kang, Kwang Ho In; Cancer Res Treat. 2017;49(1):141-149. Published online May 18, 2016; DOI: https://doi.org/10.4143/crt.2016.133

Abstract PDF PubReader ePub

Purpose
Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
Materials and Methods
Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated.
Results
A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology.
Conclusion
Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

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Eva Tsoneva, Mariela B. Vasileva-Slaveva, Stoyan G. Kostov, Angel D. Yordanov
Oncologie.2023; 25(6): 753. CrossRef
Serum Reactive Oxygen Species Modulator 1 as a Novel Predictive Biomarker for Resected Lung Adenocarcinoma: A Retrospective Pilot Study
Boksoon Chang, In Kyung Hwang, Seung Hyeun Lee
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Won Gun Kwack, Ji-Youn Sung, Seung Hyeun Lee
Frontiers in Oncology.2021;[Epub] CrossRef
Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer
Hadi Ghasemi, Mohammad Amin Amini, Atefeh Pegah, Ebrahim Azizi, Heidar Tayebinia, Shima Khanverdilou, Seyed Habibollah Mousavibahar, Aida Alizamir
Molecular Biology Reports.2020; 47(9): 6497. CrossRef
Reactive Oxygen Species Modulator 1 is Associated with Poor Survival in Patients with Non-Small Cell Lung Cancer After Stereotactic Fractionated Radiosurgery: A Retrospective Pilot Study

Moonkyoo Kong, Ji-Youn Sung, Seung Hyeun Lee
OncoTargets and Therapy.2020; Volume 13: 8173. CrossRef
Reactive oxygen species modulator 1 expression predicts lymph node metastasis and survival in early-stage non-small cell lung cancer
Taehee Kim, Yoon Jin Cha, Ji Hyun Park, Arum Kim, Yong Jun Choi, Hye Jung Park, Jung Weon Lee
PLOS ONE.2020; 15(12): e0239670. CrossRef
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Mohammad Amin Amini, Seyed Saman Talebi, Jamshid Karimi
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Seung Hyeun Lee, Myung Jae Park, Sue In Choi, Eun Joo Lee, Sang Yeub Lee, Kwang Ho In
Medicine.2017; 96(4): e5975. CrossRef

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