乙型肝炎病毒S区基因突变对乙型肝炎病毒相关性肝细胞癌患者预后的影响研究  

Mutations in the S Gene Region of Hepatitis B Virus and Postoperative Survival in Patients with Hepatitis B Virusassociated Hepatocellular Carcinoma

作　　者：吴忱思[1] 赵乐 吴建华[1] 王英南[1] 张风宾[1] 高立明[2] 赵林[3] 张卫国[4] 张瑞星[1] WU Chensi;ZHAO Yue;WU Jianhua;WANG Yingnan;ZHANG Fengbin;GAO Liming;ZHAO Lin;ZHANG Weiguo;ZHANG Ruixing(The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;First Hospital of Qinhuangdao,Qinhuangdao 066000,China;Peking Union Medical College Hospital,Beijing 100032,China;Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学第四医院,河北省石家庄市050011 [2]秦皇岛市第一医院,河北省秦皇岛市066000 [3]北京协和医院,北京市100032 [4]河北医科大学,河北省石家庄市050017

出　　处：《中国全科医学》2019年第15期1807-1811,共5页Chinese General Practice

基　　金：河北省医学科学研究重点课题计划(20180494);河北省科技厅重点研发计划项目(152777148)

摘　　要：背景我国肝癌发病率逐年上升,这主要与乙型肝炎病毒(HBV)感染流行有关,多项研究表明HBV基因突变与乙型肝炎病毒相关性肝细胞癌(HBV-HCC)患者发病密切相关,HBV S区基因突变与HBV-HCC患者术后预后的关系鲜有报道。目的通过对HBV S区基因进行测序分析,分析一般资料及HBV S区基因突变位点与HBV-HCC患者预后的关系。方法本研究于2007—2009年采集在河北医科大学第四医院行外科手术治疗的46例HBV-HCC患者的肝癌组织标本进行分析,提取DNA,针对HBV S区基因进行扩增和测序,鉴定出HBV S区基因的突变位点。记录患者的一般资料(年龄、性别、CHILD分级、基因型、肿瘤数目、门脉瘤栓、TNM分期、肿瘤大小)。分析一般资料及HBV S区基因突变位点与HBV-HCC患者术后预后的关系。结果 46例HBV-HCC患者的基因分型为25例B型、21例C型。不同门脉瘤栓、TNM分期、肿瘤大小的HBV-HCC患者3年生存率比较,差异有统计学意义(P<0.05)。共发现13个位点的突变频率>5%,其中529位点、735位点不同碱基HBV-HCC患者3年生存率比较,差异有统计学意义(P<0.05)。Cox比例风险模型分析结果显示,门脉瘤栓、529位点是HBV-HCC患者术后生存的独立影响因素(P<0.05)。结论门脉瘤栓和HBV S区529位点被确定为是与HBV-HCC患者术后预后相关的独立危险因素,这一结果有助于鉴别预后不良的HBV-HCC患者,对于提高其生存期、改善其预后具有重要意义。Background The incidence of hepatocellular carcinoma(HCC)in China is increasing year by year,which is mainly associated with the prevalence of hepatitis B virus(HBV)infection.Many studies have shown that HBV gene mutation is closely related to the pathogenesis of HBV-associated HCC.But there are few reports on the relationship between mutations in the S gene region of HBV and prognosis of patients with HBV-associated HCC.Objective To investigate the relationships of clinical factors,and HBV S gene mutations(using sequencing analysis)with postoperative survival of HBV-associated HCC patients.Methods Participants were 46 cases of HBV-associated HCC who received surgical treatment in the Fourth Hospital of Hebei Medical University during 2007 to 2009.The genomic DNA was extracted from resected HCC tissues.HBV S gene was amplified and sequenced to detect mutations.General data〔age,sex,Child-Pugh score,genotype,number of tumor entities,portal vein tumor thrombus(PVTT),TNM classification,size of tumor〕were collected.Relationships of general data,and HBV S gene mutations with the survival of the patients were analyzed.Results Of the participants,25 were found with HBV genotype B infection,and other 21 with HBV genotype C infection.Postoperative 3-year survival rates differed significantly by PVTT prevalence,TNM classification,and tumor size(P<0.05).13 loci were identified with a mutation rate of higher than 5%.In particular,postoperative 3-year survival rates significantly varied by the mutations at the 529 and 735 locus(P<0.05).Analysis with the Cox proportional hazards model found that PVTT and mutations at the 529 locus were independent influencing factors for postoperative survival(P<0.05).Conclusion PVTT prevalence and mutation at the 529 locus were identified as independent risk factors for postoperative survival in HBV-associated HCC patients,which may help to clinically identify such patients with poor prognosis,and may contribute to survival prolongation and prognosis improvement.

关 键 词：乙型肝炎病毒 肝肿瘤 癌 肝细胞 HBV S区 突变 预后 

分 类 号：R512.62[医药卫生—内科学] R730.261[医药卫生—临床医学]