Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes

作者：Zimin Song, Shuirong Lin, Xiwen Wu, Xiaoxue Ren, Yifan Wu, Haoxiang Wen, Baifeng Qian, Haozhong Lin, Yihao Huang, Chenfeng Zhao, Nian Wang, Yan Huang, Baogang Peng, Xiaoxing Li, Hong Peng, Shunli Shen · 发表于：Hepatology International · 年份：2023 · DOI：10.1007/s12072-023-10556-3 · 被引用次数：21 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Gallbladder and Bile Duct Disorders、Liver Diseases and Immunity

BACKGROUND: Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids. METHOD: The medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis. RESULTS: A total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS)...