Proteomic and single-cell landscape reveals novel pathogenic mechanisms of HBV-infected intrahepatic cholangiocarcinoma
Yifei Shen,
Shuaishuai Xu,
Chanqi Ye,
Qiong Li,
Ruyin Chen,
Wei Wu,
Qi Jiang,
Yunlu Jia,
Xiaochen Zhang,
Longjiang Fan,
Wenguang Fu,
Ming Jiang,
Jinzhang Chen,
Michael P. Timko,
Peng Zhao,
Jian Ruan
Affiliations
Yifei Shen
Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, People’s Republic of China; Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Shuaishuai Xu
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Chanqi Ye
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Qiong Li
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Ruyin Chen
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Wei Wu
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Qi Jiang
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Yunlu Jia
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Xiaochen Zhang
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Longjiang Fan
Institute of Bioinformatics, Zhejiang University, Hangzhou 310000, Zhejiang Province, People’s Republic of China
Wenguang Fu
Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People’s Republic of China
Ming Jiang
The Children’s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou 310058, Zhejiang Province, People’s Republic of China
Jinzhang Chen
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510000, Guangdong Province, People’s Republic of China
Michael P. Timko
Departments of Biology and Public Health Sciences, University of Virginia, Charlottesville, VA 22904, USA; Corresponding author
Peng Zhao
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China; Corresponding author
Jian Ruan
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou 310000, Zhejiang Province, People’s Republic of China; Corresponding author
Summary: Despite the epidemiological association between intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. A cohort of 32 HBV-infected ICC and 89 non-HBV-ICC patients were characterized using whole-exome sequencing, proteomic analysis, and single-cell RNA sequencing. Proteomic analysis revealed decreased cell-cell junction levels in HBV-ICC patients. The cell-cell junction level had an inverse relationship with the epithelial-mesenchymal transition (EMT) program in ICC patients. Analysis of the immune landscape found that more CD8 T cells and Th2 cells were present in HBV-ICC patients. Single-cell analysis indicated that transforming growth factor beta signaling–related EMT program changes increased in tumor cells of HBV-ICC patients. Moreover, ICAM1+ tumor-associated macrophages are correlated with a poor prognosis and contributed to the EMT in HBV-ICC patients. Our findings provide new insights into the behavior of HBV-infected ICC driven by various pathogenic mechanisms involving decreased cell junction levels and increased progression of the EMT program.
