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

doi:10.1016/j.isci.2023.106003

Proteomic and single-cell landscape reveals novel pathogenic mechanisms of HBV-infected intrahepatic cholangiocarcinoma

iScience. 2023 Jan 18;26(2):106003. doi: 10.1016/j.isci.2023.106003. eCollection 2023 Feb 17.

Authors

Yifei Shen^{1

2}, Shuaishuai Xu³, Chanqi Ye³, Qiong Li³, Ruyin Chen³, Wei Wu³, Qi Jiang³, Yunlu Jia³, Xiaochen Zhang³, Longjiang Fan⁴, Wenguang Fu⁵, Ming Jiang⁶, Jinzhang Chen⁷, Michael P Timko⁸, Peng Zhao³, Jian Ruan³

Affiliations

¹ Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, People's Republic of China.
² Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou 310000, Zhejiang Province, People's Republic of China.
³ 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.
⁴ Institute of Bioinformatics, Zhejiang University, Hangzhou 310000, Zhejiang Province, People's Republic of China.
⁵ Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People's Republic of China.
⁶ 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.
⁷ Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510000, Guangdong Province, People's Republic of China.
⁸ Departments of Biology and Public Health Sciences, University of Virginia, Charlottesville, VA 22904, USA.

Abstract

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.

Keywords: Cancer; Omics; Virology.