乙肝病毒致癌主要机制  

Major mechanisms of hepatitis B virus induced hepatocarcinogenesis

作　　者：赵沛 陈一凡 刘文斌 方乐天 余红平 曹广文 ZHAO Pei;CHEN Yifan;LIU Wenbin;FANG Letian;YU Hongping;CAO Guangwen(Guangxi Medical University Cancer Hospital,Nanning,Guangxi 530021,China;Faculty of Naval Medicine,Naval Medical University,Shanghai 200433,China)

机构地区：[1]广西医科大学附属肿瘤医院,广西南宁530021 [2]海军军医大学海医系,上海200433

出　　处：《上海预防医学》2022年第10期1058-1064,共7页Shanghai Journal of Preventive Medicine

基　　金：国家重点基础研究发展计划(973计划)(2015CB554000);国家自然科学基金重大研究计划集成项目(91529305);国家自然科学基金国际合作与交流项目(81520108021);国家自然科学基金面上项目(81673250);国家自然科学基金青年项目(82003538);上海市公共卫生重点学科(GWV-10.1-XK17);上海市扬帆计划项目(20YF1458800)。

摘　　要：乙型肝炎病毒(HBV)慢性感染导致肝细胞癌(HCC)发生发展的机制是典型的癌症进化发育过程。病毒复制、变异和整合是HBV促进HCC进化的主要途径。HBV复制激活并维持了慢性炎症微环境,后者诱导并选择了体细胞变异和病毒变异产生,提供进化选择压力;HBV变异通过激活关键信号通路促使细胞获得干性特征;HBV整合激活促癌基因、参与促进男性高发HCC、维持HBV慢性感染。HBV相关的生物标志物是HCC发生、预后的有效标志物。抗病毒治疗可以显著降低HCC的发生风险,HBV高危变异可以提示抗病毒治疗、改善HCC预后的效果。深入探索HBV致癌机制,有利于提供更有效的生物标志物和干预靶点,进而完善HCC的特异性预防策略。The occurrence and development of hepatocellular carcinoma(HCC)induced by chronic infection of hepatitis B virus(HBV)is a typical process of Cancer Evolution-development.Viral replication,viral mutation,and viral integration are three major mechanisms by which HBV promotes evolution of HCC.The replication of HBV induces and maintains chronic inflammatory microenvironment,that induces the generation of somatic mutation and viral mutation and provides selective pressure.HBV mutation helps cells to get stem-ness characteristics by activating key signaling pathways.HBV integration activates oncogenes,participates in the mechanism underlying the male predilection of HCC,and promotes the maintenance of chronic infection.Biomarkers related with HBV are effective predictive and prognostic markers of HCC.Anti-viral treatment significantly reduces the risk of HCC occurrence.High risk HBV mutations can be applied for predicting the effect of antiviral treatment on improving HCC survival.Continuing to exploring mechanisms of HBV induced hepatocarcinogenesis can improve the specific prophylaxis of HCC by providing more effective biomarkers and therapeutic targets.

关 键 词：乙型肝炎病毒 肝细胞癌 变异 炎症 病毒整合 

分 类 号：R183.3[医药卫生—流行病学]