Cancer Research and Treatment

Original Articles

Comprehensive Driver Mutation Landscape of DLBCL Informed by Integrated Tissue and Circulating DNA Analyses: Han Zhang, Chuanyu Hong, Xinger Gao, Yilei Shi, Chuan He, Qi Li, Ruijing Hu, Xinyuan Zhang, Xingping Lang, Wenzhuo Zhuang, Bingzong Li; Received January 26, 2026 Accepted July 11, 2026 Published online July 15, 2026; DOI: https://doi.org/10.4143/crt.2026.0093 [Accepted]

Abstract PDF: Purpose
Diffuse large B-cell lymphoma (DLBCL) is genetically heterogeneous. We aimed to define a compartment-aware driver mutation landscape of DLBCL by integrating tumor tissue and circulating cell-free DNA (cfDNA) sequencing, and to assess its biological and prognostic relevance.
Materials and Methods
Somatic mutations were analyzed from targeted sequencing of tumor tissue or bone marrow and cfDNA from peripheral blood or cerebrospinal fluid, including paired tissue–liquid samples, together with whole-genome sequencing data from TCGA. Driver genes were identified using four complementary algorithms. Functional enrichment and protein–protein interaction analyses were performed. Prognostic relevance was evaluated using multigene expression–based modeling with Cox and LASSO regression in independent cohorts.
Results
Recurrent driver alterations converged on core pathogenic pathways, including B-cell receptor signaling, NF-κB activation, epigenetic regulation, and immune escape. Twenty-two high-confidence driver genes, including PIM1, KMT2D, CD79B, B2M, TP53, MYC, and EZH2, were consistently identified across clinical cohorts and supported by TCGA data. cfDNA profiling showed substantial concordance with tissue-derived drivers while revealing gene-specific differences in mutation burden and co-mutation patterns, indicating complementary capture of clinically relevant heterogeneity. Network analysis highlighted TP53, MYC, EP300, and CREBBP as central hubs. A four-gene expression–based model (MYC, PLCL1, IRF8, LNPEP) stratified patients by overall survival and modestly improved prognostic discrimination beyond the International Prognostic Index.
Conclusion
Integrated analysis of tumor tissue and cfDNA sequencing defines a clinically relevant driver framework for DLBCL. cfDNA preserves core oncogenic signals while complementing tissue profiling, supporting refined genomic risk stratification.

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Immunotherapy

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients: Si-Qi Tang, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Lei Chen, Yuan Zhang, Ying Guo, Qing Liu, Ying Sun, Cheng Xu, Jun Ma; Cancer Res Treat. 2021;53(2):339-354. Published online November 6, 2020; DOI: https://doi.org/10.4143/crt.2020.790

Abstract PDF Supplementary Material PubReader ePub

Purpose
The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear.
Materials and Methods
Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.
Results
Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).
Conclusion
This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Citations

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Gastrointestinal cancer

Long Non-coding RNA CASC15 Promotes Intrahepatic Cholangiocarcinoma Possibly through Inducing PRDX2/PI3K/AKT Axis: Yuan Zhang, Lufei Zhang, Sinan Lu, Yucheng Xiang, Cheng Zeng, Tianyu He, Yuan Ding, Weilin Wang; Cancer Res Treat. 2021;53(1):184-198. Published online October 5, 2020; DOI: https://doi.org/10.4143/crt.2020.192

Abstract PDF Supplementary Material PubReader ePub

Purpose
Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear.
Materials and Methods
Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry.
Results
CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway.
Conclusion
CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Citations

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A novel interpretable machine learning framework integrating clinicopathological and radiomic features for early recurrence prediction in mass-forming intrahepatic cholangiocarcinoma
Xiao-li Deng, Chongze Yang, Lan-hui Qin, Xue-feng Lin, Fen Zhong, Jin-yuan Liao
Cancer Imaging.2026;[Epub] CrossRef
CASC15 Promotes Cholangiocyte Proliferation and Liver Fibrosis by Regulating the HNRNPU-IGFBP3 Axis in Biliary Atresia
Yao Lu, Zhongxian Zhu, Yufei Zhu, Wei Zhu, Ruyi Zhang, Zequan Ding, Hua Xie, Weibing Tang
Digestive Diseases and Sciences.2026; 71(7): 2926. CrossRef
Mechanisms of Action and Biomarker Potential of ncRNAs in Hepatocellular Carcinoma and Liver Fibrosis: A Review
Eun Jung Sohn, Sae-Ock Oh, Suraiya Saleem
Analytical Cellular Pathology.2026;[Epub] CrossRef
Mri-based Ki-67 prediction for intrahepatic cholangiocarcinoma: Risk stratification and treatment efficacy prediction
Beixuan Zheng, Lingsong Zhou, Kai Liu, Jing Han, Bin Wang, Ruofan Sheng, Mengsu Zeng
European Journal of Radiology.2026; 199: 112790. CrossRef
Involvement of the PRDX family and its clinical functions in different types of gastrointestinal cancer (Review)
Zhou Zhang, Yujie Wang, Yuhao Liu, Haizhen Wu, Xiaopeng Xu, Kai Wang, Chen He, Chen Qian
Oncology Reports.2025; 54(2): 1. CrossRef
Advances in Multi-Omics Research on Biomarkers of Intrahepatic Cholangiocarcinoma
Jingxue Yang, Jintong Na, Tieliu Shi, Xiyu Liu
Current Issues in Molecular Biology.2025; 47(11): 905. CrossRef
The LINC00519/hsa- miR- 22- 3p/MECOM Axis Accelerates Intrahepatic Cholangiocarcinoma Progression through PI3K/AKT Signaling
Zhuxin Gu, Yanjun Sun, Fajing Chen, Weiwei Gu, Xiaohua Lu, Suming Zhao, Qinan Geng, Yang Yang
Molecular Cancer Research.2025; 23(11): 913. CrossRef
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Zhangdi Yan, Lixin Du, Xiaotong Zhang, Yunjia Liu, Yuankun Zhang, Jian Deng, Zongli Zhang, Yongchang Tang
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Qingshan Cai, Dongyang Wu, Yueling Shen, Shudong Li, Liyou Liu, Dong Liu, Yong Li, Xiaonan Chen, Limin Wang, Jianxing Zheng
Medicine.2024; 103(5): e35859. CrossRef
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Mete Ucdal, Ayse Burus, Basak Celtikci
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A review on the role of ncRNAs in the pathogenesis of cholangiocarcinoma
Soudeh Ghafouri-Fard, Arash Safarzadeh, Bashdar Mahmud Hussen, Mohammad Taheri, Majid Samsami
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Weiwei Chen, Wenqi Qian, Jun Nie, Mintao Dai
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Long Non-Coding RNAs as Molecular Biomarkers in Cholangiocarcinoma
Yanhua Wu, Khizar Hayat, Yufei Hu, Jianfeng Yang
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Wen Chao Li, Li Liu, Zhen Dong Wang, Hui Chen, Guang Liu, Zhi Chun Feng
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Pei-Jian Zhang, Meng-Dong Liu, Fang-Yong Fan, Ke-Xia Liu
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LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151–5p/WNT7A axis
Dongfang Bai, Chong Guo, Aimin Wang, Guolong Pang, Jing Gao, Chuan Wang, Dapeng Zhao, Jie Yang, Jianmin Ren
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Chen Chen, Linjing Wang, Li Wang, Qi Liu, Chunying Wang
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Li Guo, Yuyang Dou, Yifei Yang, Shiqi Zhang, Yihao Kang, Lulu Shen, Lihua Tang, Yaodong Zhang, Changxian Li, Jun Wang, Tingming Liang, Xiangcheng Li
Computational and Structural Biotechnology Journal.2021; 19: 5722. CrossRef

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Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area: Cheng Xu, Shi-Ping Yang, Yuan Zhang, Ling-Long Tang, Guan-Qun Zhou, Xu Liu, Yan-Ping Mao, Rui Guo, Wen-Fei Li, Lei Chen, Ai-Hua Lin, Ying Sun, Jun Ma; Cancer Res Treat. 2018;50(3):777-790. Published online July 24, 2017; DOI: https://doi.org/10.4143/crt.2017.255

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLR_min). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLR_min on OS/DFS.
Results
Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLR_min (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLR_min ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect.
Conclusion
Occurrence of neutropenia, number of myelosuppression events, and high post-NLR_min during PF/TP IC-1 have prognostic value for poor survival in LANPC.

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Jun Wang, Baosheng Li
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Yuanji Xu, Zijie Wu, Wangzhong Ye, Youping Xiao, Wei Zheng, Qinyan Chen, Penggang Bai, Zhizhong Lin, Chuanben Chen
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Time-to-Event Supervised Genetic Algorithm Enables Induction Chemotherapy Decision Making for Nasopharyngeal Carcinoma
Demin Liu, Haojiang Li, Liyang Wu, Shuchao Chen, Tianqiao Zhang, Wenjie Huang, Guangying Ruan, Sai Li, Lizhi Liu, Hongbo Chen
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Prognostic value of post-radiotherapy neutrophil-to-lymphocyte ratio in locally advanced nasopharyngeal carcinoma
Dan Ou, Xiaoshen Wang, Mingyao Wu, Fen Xue, Yujiao Li, Chaosu Hu, Xiayun He
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