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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 预览

Mutations in the S Gene Region of Hepatitis B Virus and Postoperative Survival in Patients with Hepatitis B Virusassociated Hepatocellular Carcinoma
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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.
作者 吴忱思 赵乐 吴建华 王英南 张风宾 高立明 赵林 张卫国 张瑞星 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)
出处 《中国全科医学》 CAS 北大核心 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).
关键词 乙型肝炎病毒 肝肿瘤 肝细胞 HBV S区 突变 预后 Hepatitis B virus Liver neoplasms Carcinoma,hepatocellular S gene region of HBV Mutation Prognosis
作者简介 通信作者:张卫国,副教授;E-mail:hebzhang@yeah.net;通信作者:张瑞星,教授;E-mail:zrx@ medmail.com.cn.
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