HCC 是最常见的原发性肝癌类型，是世界范围内常见的恶性肿瘤。由于乙肝病毒感染率高，每年全球新增肝癌病例中约有一半发生在中国，包括香港。 HBV DNA 整合到人类基因组中，破坏内源性肿瘤抑制/调节基因或增强原癌基因的活性。检查不同的基于 NGS 的数据库将有助于对 HBV 整合提供更加公正和全面的调查。我们的目的是利用不同区域队列的公开数据集来确定样本队列之间整合事件的差异情况，组织类型、染色体位置、个体宿主和病毒基因以及基因位置。通过比较 HCC 肿瘤与非肿瘤肝脏，以基因无关和基因依赖的方式描绘了 HBV 整合的情况。此外，我们对 HBV-TERT 整合如何导致 TERT 激活进行了机制研究，并根据 HBV 整合的克隆差异状况得出了预测患者预后的评分。我们的研究揭示了 HBV 整合的不同水平的克隆富集，并确定了机制见解和预后生物标志物。这加强了我们对 HBV 相关肝癌发生的理解。版权所有 © 2024 作者。由 Wolters Kluwer Health, Inc. 出版

HCC is the most common type of primary liver cancer and is a common malignancy worldwide. About half of all new liver cancers worldwide each year occur in China, including Hong Kong, due to a high prevalence of HBV infection. HBV DNA integrates into the human genome, disrupting the endogenous tumor suppressors/regulatory genes or enhancing the activity of proto-oncogenes. It would be useful to examine the different NGS-based databases to provide a more unbiased and comprehensive survey of HBV integration.We aimed to take advantage of publicly available data sets of different regional cohorts to determine the disparity landscapes of integration events among sample cohorts, tissue types, chromosomal positions, individual host, and viral genes, as well as genic locations. By comparing HCC tumors with non tumorous livers, the landscape of HBV integration was delineated in gene-independent and gene-dependent manners. Moreover, we performed mechanistic investigations on how HBV-TERT integration led to TERT activation and derived a score to predict patients' prognostication according to their clonal disparity landscape of HBV integration.Our study uncovered the different levels of clonal enrichment of HBV integration and identified mechanistic insights and prognostic biomarkers. This strengthens our understanding of HBV-associated hepatocarcinogenesis.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.