Shen Yifei, Xu Shuaishuai, Ye Chanqi, Li Qiong, Chen Ruyin, Wu Wei, Jiang Qi, Jia Yunlu, Zhang Xiaochen, Fan Longjiang, Fu Wenguang, Jiang Ming, Chen Jinzhang, Timko Michael P, Zhao Peng, Ruan Jian
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.
iScience. 2023 Jan 18;26(2):106003. doi: 10.1016/j.isci.2023.106003. eCollection 2023 Feb 17.
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.
尽管肝内胆管癌（ICC）与乙型肝炎病毒（HBV）感染之间存在流行病学关联，但对相关致癌作用知之甚少。使用全外显子测序、蛋白质组分析和单细胞RNA测序对32例HBV感染的ICC患者和89例非HBV-ICC患者进行了特征分析。蛋白质组分析显示，HBV-ICC患者的细胞间连接水平降低。细胞间连接水平与ICC患者的上皮-间质转化（EMT）程序呈负相关。免疫图谱分析发现，HBV-ICC患者中存在更多的CD8 T细胞和Th2细胞。单细胞分析表明，HBV-ICC患者肿瘤细胞中与转化生长因子β信号相关的EMT程序变化增加。此外，ICAM1肿瘤相关巨噬细胞与预后不良相关，并促进了HBV-ICC患者的EMT。我们的研究结果为受多种致病机制驱动的HBV感染ICC的行为提供了新的见解，这些机制包括细胞连接水平降低和EMT程序进展增加。
