机构：[1]Department of Liver Surgery & Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China四川大学华西医院[2]Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China[3]Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China[4]Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China[5]The Fifth Affiliated Hospital, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China[6]Department of Research and Development, Jiangsu Gaomei Genomics, Nanjing, China[7]Department of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China[8]Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma (ICC) patients. In this study, we developed a methylation signature that precisely predicts overall survival (OS) after surgery.An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing (WGBS) was conducted for two independent cohorts (discovery cohort, n=164; validation cohort, n=170) from three hepatobiliary centers in China. By referring to differentially methylated regions (DMRs), we proposed the concept of prognostically methylated regions (PMRs), which were composed of consecutive prognostically methylated CpGs (PMCs). Using machine learning strategies (Random Forest and the least absolute shrinkage and selector regression), a prognostic methylation score (PMS) was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort.The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74, respectively. In the whole cohort, the PMS was an independent predictor of OS [hazard ratio (HR) =8.12; 95% confidence interval (CI): 5.48-12.04; P<0.001], and the C-index (0.78) of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine (JHUSM) nomogram (0.69, P<0.001), the Eastern Hepatobiliary Surgery Hospital (EHBSH) nomogram (0.67, P<0.001), American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (0.61, P<0.001), and MEGNA prognostic score (0.60, P<0.001). The patients in quartile 4 of PMS could benefit from adjuvant therapy (AT) (HR =0.54; 95% CI: 0.32-0.91; log-rank P=0.043), whereas those in the quartiles 1-3 could not. However, other nomograms and staging system failed to do so. Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors, pathway activation, and immune microenvironment.The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients, and might facilitate decisions in treatment of ICC patients.2023 Hepatobiliary Surgery and Nutrition. All rights reserved.
基金：
This work was supported by The National
Key Technologies R&D Program of China (No.
2018YFC1106800), The 1.3.5 project for disciplines of
excellence, West China Hospital, Sichuan University (No.
ZYJC18008), and The Natural Science Foundation of
China (Nos. 91859105, 81773012, 81872004, 81802302 and
81902401).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|2 区医学
小类|2 区营养学2 区外科3 区胃肠肝病学
最新[2023]版：
大类|2 区医学
小类|2 区营养学2 区外科3 区胃肠肝病学
第一作者：
第一作者机构：[1]Department of Liver Surgery & Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Liver Surgery & Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China[2]Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China[3]Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China[5]The Fifth Affiliated Hospital, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China[6]Department of Research and Development, Jiangsu Gaomei Genomics, Nanjing, China[8]Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China[*1]Department of Liver Surgery & Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.[*2]o. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China[*3]Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China[*4]The Fifth Affiliated Hospital, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.[*5]Department of Liver Surgery & Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
推荐引用方式(GB/T 7714)：
Chen Xing,Dong Liangqing,Chen Lu,et al.Epigenome-wide development and validation of a prognostic methylation score in intrahepatic cholangiocarcinoma based on machine learning strategies[J].Hepatobiliary surgery and nutrition.2023,12(4):478-494.doi:10.21037/hbsn-21-424.
APA：
Chen Xing,Dong Liangqing,Chen Lu,Wang Yuan,Du Jinpeng...&Zeng Yong.(2023).Epigenome-wide development and validation of a prognostic methylation score in intrahepatic cholangiocarcinoma based on machine learning strategies.Hepatobiliary surgery and nutrition,12,(4)
MLA：
Chen Xing,et al."Epigenome-wide development and validation of a prognostic methylation score in intrahepatic cholangiocarcinoma based on machine learning strategies".Hepatobiliary surgery and nutrition 12..4(2023):478-494
