肝细胞癌患者肝癌组织中乙型肝炎病毒核心启动子变异分析

Analysis of hepatitis B virus core promoter mutations in liver tissues of patients with hepatocellular carcinoma

目的深入了解乙型肝炎(乙肝)病毒(HBV)核心启动子(core promoter,CP)变异在肝细胞癌(hepatocellular carcinoma,HCC)患者肝癌组织标本中的发生情况。方法分别对北京佑安医院52例肝细胞癌患者,45例肝硬化(cirrhosis of liver,LC)和25例慢性乙肝(chronic hepatitis B,CH)患者肝组织标本中HBV前C区和CP区进行克隆测序,对核心启动子变异情况进行统计分析。结果与慢性乙型肝炎和肝硬化比较,G1613A、A1727C、A1762T、G1764A和1896A突变比例在肝细胞癌患者中更高(P<0.05)。肝细胞癌组中核心启动子不同调控区的突变发生率显著高于慢性乙肝和肝硬化组(P<0.05)。结论从组织学角度进一步支持肝细胞癌组中核心启动子区突变的高流行率,特别是A1762T/G1764A双突变可以作为肝细胞癌发生的预测指标,其他突变位点对于病毒复制、转录以及肝细胞癌发生的作用,有待进一步研究确证。

Objective To explore hepatitis B virus （HBV） core promoter mutations in the liver tissue of hepa- tocellular carcinoma （HCC） patients and compare with liver cirrhosis （LC） and chronic hepatitis B （CHB）. Methods HBV pre-C and core promoter （CP） regions in the liver tissues of 52 HCC, 45 LC and 25 CHB pa tients were cloned and sequenced, and then the core promoter mutations were analyzed. Results Comparing to CHB and LC, HCC patients had a higher proportion of G1613A, A1727C, A1762T, G1764A and 1896A mutations （P^0.05）. The mutation rate of the core promoter regulatory regions in HCC group was signifi- cantly higher than that in the LC and CHB groups （P^0.05）. Conclusions Our histology data support that the HBV core promoter region mutations in the HCC group are at a higher prevalence; A1762T/G1764A double mutations can be used as a predictor of HCC.