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
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.