广西医科大学学报2026，Vol.43Issue(4)：497-504,8.DOI:10.16190/j.cnki.45-1211/r.2026.04.006
肝细胞癌乙型肝炎病毒整合的靶基因与断点特征分析
Analysis of target genes and breakpoint characteristics of HBV integration in hepatocellular carcinoma
摘要
Abstract
Objective:To identify common hepatitis B virus(HBV)integration target genes and fragments in the liver tissues from patients with HBV-related hepatocellular carcinoma(HCC),thereby providing a theoretical ba-sis for optimizing the early screening strategies of liver cancer.Methods:Liquid-phase hybridization capture se-quencing with HBV probes was applied to detect HBV integration in the cancerous and adjacent non-cancerous tissues from 26 patients with HBV-related HCC,and the patterns of HBV integration as well as their as-sociation with the pathogenesis of early-stage HCC were explored.Targeted amplification and Sanger sequencing were performed to validate HBV integration within the FN1 gene locus in a subset of samples from adjacent non-cancerous tissues.Results:The number of HBV integration breakpoints detected in the cancerous tissues was sig-nificantly lower than that in the adjacent non-cancerous tissues.In early-stage HCC cases,HBV integration was predominantly observed in the adjacent non-cancerous tissues(P＜0.05).TERT was the most common target gene of HBV integration in the cancerous tissues,whereas FN1 was the predominant target gene of HBV integra-tion in the adjacent non-cancerous tissues.HBV integrated fragments were primarily clustered in the 300-500 bp and 1300-1900 bp regions of the HBV genome,and the regions encompassed the entire HBX gene,Precore/core gene,and partial S genes.Finally,the precise integration of HBV within the FN1 gene locus was validated using polymerase chain reaction(PCR)and Sanger sequencing.The integration breakpoints of target genes in the cancerous tissues were mostly located in exons,whereas those in the adjacent non-cancerous tissues were mostly located in introns.Conclusion:HBV integration is significantly enriched in the adjacent non-cancerous tissues of early-stage HCC,with FN1 being the most common target gene.Since the integrated HBV fragments can be released into the bloodstream,this study provides a preliminary theoretical basis for the subsequent development of non-invasive early screening techniques to detect HBV integration based on plasma cell-free DNA(cfDNA).关键词
乙型肝炎病毒相关肝细胞癌/早期肝癌筛查/乙型肝炎病毒整合/血浆游离DNA/FN1基因/整合断点/靶基因/TERT基因Key words
hepatitis B virus-related hepatocellular carcinoma/early-stage hepatocellular carcinoma screening/hepatitis B virus integration/plasma cell-free DNA/FN1 gene/integration breakpoints/target genes/TERT gene分类
医药卫生引用本文复制引用
蔡冬梅,丘洁,安三春,陶治宇,陈晓梅,吕瑞博,张朝钧,邓伟..肝细胞癌乙型肝炎病毒整合的靶基因与断点特征分析[J].广西医科大学学报,2026,43(4):497-504,8.基金项目
国家自然科学基金资助项目(82160638) （82160638）
