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

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机构： [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

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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.© 2023 The Author(s).

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大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

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大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

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Q1 MULTIDISCIPLINARY SCIENCES

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Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 4.6 最新[2023版] 5 最新五年平均 4.6 出版当年[2023版] 5 出版当年五年平均 5.8 出版前一年[2022版]

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第一作者机构： [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

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