HBVpreC/C区基因突变与原发性肝癌预后的关系

摘要

目的 研究乙型肝炎病毒(hepatitis B virus,HBV)preC/C区基因突变与原发性肝癌患者预后的关系.方法 收集81例乙型肝炎病毒相关性肝细胞肝癌(hepatitis B virus associated hepatocellular carcinoma,HBV-HCC)患者的癌组织并提取基因组DNA,对HBV preC/C区基因进行扩增和测序,并根据NCBI数据库鉴定出其突变位点,运用Kaplan-Meier和Cox回归等方法分析HBV-HCC患者的临床资料、突变位点与其术后生存期之间的关系.结果 门脉瘤栓、肿瘤分期和肿瘤大小是与HBV-HCC患者术后生存相关的独立危险因素.1915、2134、2176、2221和2260突变位点被确定为预测HBV-HCC患者生存相关的独立危险因子,1979和2245突变位点与HBV-HCC患者生存具有临界统计学差异.结论 门脉瘤栓、肿瘤分期和肿瘤大小以及HBV preC/C区基因的以上7个突变位点被确定为与肝癌患者术后预后相关的独立危险因素.%Objective To investigate the relationship between the mutations in precore/ core (preC/ C) region of hepatitis B virus ( HBV) gene and the postoperative survival in patients with hepatocellular carcinoma. Methods A total of 81 cases in HBV associated hepatocellular carcinoma (HBV-HCC) patients with cancer tissue genomic DNA were extracted. The preC/ C region of HBV was amplified and sequenced, and survival-associated HBV mutations were identified according to the NCBI database. The relationships between the mutations in the preC/ C region and HCC survival was analyzed with the Kaplan-Meier method and the Cox proportional hazards model. Eleven mutational sites were identified as statistically significant independent predictors of HBV-HCC postoperative survival. Results The portal vein thrombosis, tumor TNM classification and size were identified as statistically significant independent predictors of survival in HBV-HCC patients. In the research, we found that seven mutational sites in preC/ C region of HBV were associated with independent risk factors for postoperative survival in patients of HBV-HCC. The following five mutational sites were identified as statistically significant independent predictors of HBV-HCC survival:1915,2134,2176,2221,2260. The mutational site of 1979 and 2245 were identified for the association with survival at a borderline significance level. Conclusions The portal vein thrombosis, tumor TNM classification,size and seven mutational sites in the PreC/ C region were identified as independent predictors of postoperative survival in HCC patients.