Cancer Research and Treatment

Original Articles

Tumor-Intrinsic Hepatocyte Arm-Level Genomic States Shape Immunotherapy Response Heterogeneity in Hepatocellular Carcinoma: Kyuhyung Choi, Hojun Sung, Sunmin Kim, Tae-Min Kim; Received March 10, 2026 Accepted June 15, 2026 Published online June 17, 2026; DOI: https://doi.org/10.4143/crt.2026.0245 [Accepted]

Abstract PDF: Purpose
Bulk transcriptomic biomarkers for immune checkpoint inhibitor (ICI) response in hepatocellular carcinoma (HCC) often lack reproducibility because bulk RNA sequencing captures composite signals from malignant, immune, and stromal compartments. Variability in tumor purity and malignant cell composition can confound immune-based interpretations. We developed an integrative framework combining single-cell–derived digital cytometry with inference of tumor-intrinsic genomic states to better interpret transcriptomic variation associated with ICI response.
Materials and Methods
Single-cell RNA sequencing data from HCC tumors (GSE206325) were used to construct a nine–cell-type signature matrix for CIBERSORTx deconvolution and to infer chromosome arm-level copy number variation in malignant hepatocytes using inferCNV. Signature stability was evaluated through pseudobulk reconstruction and gradient simulations. Digital cytometry was applied to three bulk RNA-seq ICI cohorts (GSE202069, GSE215011, and GSE279750). Arm-level alterations were projected onto bulk transcriptomes by mapping arm-associated genes, standardizing expression within samples, and aggregating direction-adjusted Q90 statistics into a composite arm-axis score.
Results
Digital cytometry revealed cohort-dependent variability in malignant hepatocyte dominance and limited reproducibility of immune fraction differences. Differential expression analysis also showed poor cross-cohort concordance. InferCNV identified recurrent arm-level alterations (1q/8q gain, 12p/13q loss), defining a continuous genomic axis. In pooled analysis (n=36), integrating the arm-axis score with PD-L1 improved discrimination (AUC 0.775; 95% CI, 0.602–0.920). In TCGA-LIHC (n=361), arm-level burden was inversely associated with cytolytic activity and positively associated with proliferation.
Conclusion
Tumor-intrinsic hepatocyte genomic states provide complementary predictive information beyond immune activation alone and may help explain heterogeneity in ICI response across HCC cohorts.

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Lung and Thoracic cancer

The Role of Circulating Tumor Cell as a Promising Biomarker in the Evaluation of Pulmonary Nodules: A Prospective Study: Shijie Wang, Changdan Xu, Xiaohong Xu, Weipeng Shao, Guohui Wang, Xiongtao Yang, Liwei Gao, Feng Teng, Hongliang Sun, Yue Zhao, Hongxiang Feng, Guangying Zhu; Cancer Res Treat. 2026;58(1):128-140. Published online March 27, 2025; DOI: https://doi.org/10.4143/crt.2024.841

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Purpose
Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis.
Materials and Methods
Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted.
Results
A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases.
Conclusion
CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Citations

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Integrated CT Radiomics and Circulating Tumor Cell Analysis in Predicting Lung Adenocarcinoma Invasion: A Dual-Center Study with Implications for Personalized Treatment
Qingtao Zhao, Runzhe Wang, Qingxin Zhao, Dahu Ren, Lingxin Kong, Xiaopeng Zhang, Guochen Duan
OncoTargets and Therapy.2026; Volume 19: 1. CrossRef
Establishment of a multi-targeted magnetic combined enrichment system for circulating tumor cells in gastric cancer and analysis of their genomic profiles
Linfei Huang, Yuelu Ruan, Lei Zhu, Jing Xu
Journal of Biomaterials Applications.2026;[Epub] CrossRef

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Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Citations

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Comprehensive analysis of FGFR2b and its correlation with essential biomarkers, intratumoral heterogeneity, and survival in advanced gastric cancer
Yoonjin Kwak, Tae-Yong Kim, Hye Seung Lee, Soo Kyung Nam, Hyeon Jeong Oh, Do-Youn Oh, Seock-Ah Im
British Journal of Cancer.2026; 134(10): 1429. CrossRef
Genomic and transcriptomic analyses of residual invasive triple-negative breast cancer after neoadjuvant chemotherapy in the prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab plus capecitabine compared to capecitabine; KCSG-B
S.-A. Im, K. Park, J. Koh, C. Park, K.H. Jung, J. Lee, H.K. Ahn, A. Lee, S.H. Sim, M.H. Kim, J.H. Kim, J.H. Kim, K.E. Lee, K.H. Park, J. Bae, M.H. Lee, S. Lim, H.J. Kim, D.-W. Lee, J.H. Jeong, K.S. Lee, J. Sohn, K.J. Suh, J.-Y. Kim, Y.J. Cha, J. Moon, C.-
ESMO Open.2025; 10(10): 105804. CrossRef

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