Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

The Feasibility of Using Biomarkers Derived from Circulating Tumor DNA Sequencing as Predictive Classifiers in Patients with Small-Cell Lung Cancer: Yu Feng, Yutao Liu, Mingming Yuan, Guilan Dong, Hongxia Zhang, Tongmei Zhang, Lianpeng Chang, Xuefeng Xia, Lifeng Li, Haohua Zhu, Puyuan Xing, Hongyu Wang, Yuankai Shi, Zhijie Wang, Xingsheng Hu; Cancer Res Treat. 2022;54(3):753-766. Published online October 5, 2021; DOI: https://doi.org/10.4143/crt.2021.905

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Purpose
To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes.
Materials and Methods
Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]).
Results
Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%.
Conclusion
Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.

Citations

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Cell-free and extrachromosomal DNA profiling of small cell lung cancer
Roya Behrouzi, Alexandra Clipson, Kathryn L. Simpson, Fiona Blackhall, Dominic G. Rothwell, Caroline Dive, Florent Mouliere
Trends in Molecular Medicine.2025; 31(1): 64. CrossRef
Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration
Changshu Li, Jun Shao, Peiyi Li, Jiaming Feng, Jingwei Li, Chengdi Wang
Cancer Letters.2023; 577: 216365. CrossRef
Prognostic and predictive impact of molecular tumor burden index in non‐small cell lung cancer patients
Fan Yang, Min Tang, Liang Cui, Jing Bai, Jiangyong Yu, Jiayi Gao, Xin Nie, Xu Li, Xuefeng Xia, Xin Yi, Ping Zhang, Lin Li
Thoracic Cancer.2023; 14(31): 3097. CrossRef
Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets
Ugo Testa, Elvira Pelosi, Germana Castelli
Onco.2022; 2(3): 186. CrossRef

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Prognostic Value of TP53 Mutation for Transcatheter Arterial Chemoembolization Failure/Refractoriness in HBV-Related Advanced Hepatocellular Carcinoma: Miao Xue, Yanqin Wu, Wenzhe Fan, Jian Guo, Jialiang Wei, Hongyu Wang, Jizhou Tan, Yu Wang, Wang Yao, Yue Zhao, Jiaping Li; Cancer Res Treat. 2020;52(3):925-937. Published online March 30, 2020; DOI: https://doi.org/10.4143/crt.2019.533

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Purpose
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Citations

Citations to this article as recorded by

Therapeutic efficacy and prognostic indicators in re-resection for recurrent hepatocellular carcinoma: Insights from a retrospective study
Qi Fan, Pengcheng Wei, Delin Ma, Qian Cheng, Jie Gao, Jiye Zhu, Zhao Li
Surgery Open Science.2025; 23: 16. CrossRef
TP53 Mutation Predicts Worse Survival and Earlier Local Progression in Patients with Hepatocellular Carcinoma Treated with Transarterial Embolization
Ken Zhao, Anita Karimi, Luke Kelly, Elena Petre, Brett Marinelli, Erica S. Alexander, Vlasios S. Sotirchos, Joseph P. Erinjeri, Anne Covey, Constantinos T. Sofocleous, James J. Harding, William Jarnagin, Carlie Sigel, Efsevia Vakiani, Etay Ziv, Hooman Yar
Current Oncology.2025; 32(1): 51. CrossRef
Clinical Therapy: HAIC Combined with Tyrosine Kinase Inhibitors and Programmed Cell Death Protein-1 Inhibitors versus HAIC Alone for Unresectable Hepatocellular Carcinoma
Baokun Liu, Lujun Shen, Wen Liu, Zhiyong Zhang, Jieqiong Lei, Zhengguo Li, Qinquan Tan, Hengfei Huang, Xingdong Wang, Weijun Fan
Journal of Hepatocellular Carcinoma.2024; Volume 11: 1557. CrossRef
Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE
Libo Wang, Jiahui Cao, Zaoqu Liu, Shitao Wu, Yin Liu, Ruopeng Liang, Rongtao Zhu, Weijie Wang, Jian Li, Yuling Sun
Hepatology Communications.2024;[Epub] CrossRef
Development and validation of survival prediction models for patients with hepatocellular carcinoma treated with transcatheter arterial chemoembolization plus tyrosine kinase inhibitors
Kun Huang, Haikuan Liu, Yanqin Wu, Wenzhe Fan, Yue Zhao, Miao Xue, Yiyang Tang, Shi-Ting Feng, Jiaping Li
La radiologia medica.2024; 129(11): 1597. CrossRef
Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE
Kun Huang, Yanqin Wu, Wenzhe Fan, Yue Zhao, Miao Xue, Haikuan Liu, Yiyang Tang, Jiaping Li
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11247. CrossRef
Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score
Jia-Wei Zhong, Dan-Dan Nie, Ji-Lan Huang, Rong-Guang Luo, Qing-He Cheng, Qiao-Ting Du, Gui-Hai Guo, Liang-Liang Bai, Xue-Yun Guo, Yan Chen, Si-Hai Chen
Discover Oncology.2023;[Epub] CrossRef
Mechanisms of Pharmacoresistance in Hepatocellular Carcinoma: New Drugs but Old Problems
Jose J.G. Marin, Marta R. Romero, Elisa Herraez, Maitane Asensio, Sara Ortiz-Rivero, Anabel Sanchez-Martin, Luca Fabris, Oscar Briz
Seminars in Liver Disease.2022; 42(01): 087. CrossRef
Non-Apoptotic Programmed Cell Death-Related Gene Signature Correlates With Stemness and Immune Status and Predicts the Responsiveness of Transarterial Chemoembolization in Hepatocellular Carcinoma
Guixiong Zhang, Wenzhe Fan, Hongyu Wang, Jie Wen, Jizhou Tan, Miao Xue, Jiaping Li
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Plasma arginase-1 as a predictive marker for early transarterial chemoembolization refractoriness in unresectable hepatocellular carcinoma
Wei-Li Xia, Shi-Jun Xu, Yuan Guo, Xiao-Hui Zhao, Hong-Tao Hu, Yan Zhao, Quan-Jun Yao, Lin Zheng, Dong-Yang Zhang, Chen-Yang Guo, Wei-Jun Fan, Hai-Liang Li
Frontiers in Oncology.2022;[Epub] CrossRef
Useful genes for predicting the efficacy of transarterial chemoembolization in hepatocellular carcinoma
Yuan Guo, Hongtao Hu, Shijun Xu, Weili Xia, Hailiang Li
Journal of Cancer Research and Therapeutics.2022; 18(7): 1860. CrossRef
Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma
Tian-Cheng Wang, Tian-Zhi An, Jun-Xiang Li, Zi-Shu Zhang, Yu-Dong Xiao
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef
Transcatheter arterial chemoembolization followed by surgical resection for hepatocellular carcinoma: a focus on its controversies and screening of patients most likely to benefit
Zhan-Qi Wei, Yue-Wei Zhang
Chinese Medical Journal.2021; 134(19): 2275. CrossRef
Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma
Young Chang, Soung Won Jeong, Jae Young Jang, Yong Jae Kim
International Journal of Molecular Sciences.2020; 21(21): 8165. CrossRef

8,830 View
150 Download
15 Web of Science
14 Crossref

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