HBV基因BCP区A1762T/G1764A双突变与肝癌术后复发或转移的相关研究

Effects of hepatitis B virus DNA mutation at 1762/1764 in the basic core promoter on metastasis or recurrence of hepatocellular carcinoma after hepalobectomy

目的:探讨HBV基因基本核心启动子区1762/1764双突变对肝细胞肝癌术后复发或转移的影响。方法:按队列研究设计方案,对211例HCC术后病例行两年随访,收集患者一般资料、病史、体征、生化和影像检查、HBV病毒学指标等结果,提取血清,利用巢式PCR法扩增HBV BCP区和S区,双向测序,确定HBV基因型及1762/1764位点,Log-Rank法单因素分析1762/1764双突变及相关因素对HCC术后复发或转移的影响,单因素分析显示有统计差异的指标进行多因素COX回归分析。结果:共187例患者进行有效随访,119例于术后2年内出现HCC复发或转移,单因素分析显示,与HCC术后复或转移相关因素有初始肿瘤大小、肿瘤包膜和门脉癌栓存在与否、γ-谷氨酰转移酶、HBV DNA水平和BCP区双突变,BCP双突变阳性组术后复发转移中位时间为9个月(95%CI:7.922-10.078),COX回归分析显示初始肿瘤大小、肿瘤包膜和BCP区双突变与肿瘤术后复发和转移独立相关[OR(95%CI),P分别为25.946(2.819-57.149),0.007;8.741(1.896-21.218),0.033和27.966(8.167-58.132),0.003]。结论:HBV BCP区1762/1764双突变阳性、初始肿瘤较大及肿瘤无包膜可以预测乙肝相关HCC术后复发转移率增高,且复发转移时间较早。

Objective： To study the effects of hepatitis B virus DNA mutation at 1762/1764 in the basic core promoter （BCP） on metastasis or recurrence of hepatocellular carcinoma （HCC） after hepalobectomy. Methods： Two-hundred and eleven patients with HCC were included in this study after hepalobectomy. Initial demographic data, clinical history, physical examination, biochemical tests, imaging examination and serum HBV DNA level was recorded. The DNA sequences of the S region and BCP region of HBV was determined by direct sequencing following nested-PCR amplification. Prognostic factors were assessed using a univariate Kaplan-Meier analysis and a multivariate Cox proportional hazards model. Results： Of the 187 HCC cases, 119 experienced tumor metastasis or recur- rence. The univariate analysis showed that a higher metastasis or recurrence rate was associated with larger tumor size, no intact capsule, positive portal vein tumor thrombosis, higher level of gamma-glutamyl transpeptidase, higher level of HBV DNA and positive BCP mutation. The median metastasis or recurrence time for patients with positive BCP mutation was 9 months （95% Cl：7.922-10.078）. Cox analysis indicated that larger tumor size, no intact capsule and positive BCP 1762/1764 double mutations were indepent risk factors for HCC recurrence or metastasis [OR （95% CI）, P： 25.946 （2.819-57.149）, 0.007;8.741 （1.896-21.218）, 0.033 and 27.966 （8.167-58.132）, 0.003, repsectively]. Conculsion： Infection with HBV carrying the positive BCP 1762/1764 double mutation, initial larger tumor volume as well as no intact capsule around the tumor independently predict the development of HCC metastasis or recurrence and ealier time for metastasis or recurrence after hepalobectomy.