原发性肝细胞癌患者乙型肝炎病毒X基因突变检测及其临床意义  

Associations between hepatitis B virus x gene mutations and hepatocellular carcinoma

作　　者：王淼[1] 胡艳芳[1] 史为涛[1] 王勤英[1] 

机构地区：[1]山西医科大学第一临床医院感染病科,太原030001

出　　处：《中华肝脏病杂志》2015年第8期599-603,共5页Chinese Journal of Hepatology

基　　金：山西省教育厅资助项目（20121006）

摘　　要：目的检测原发性肝癌患者和慢性HBV感染者HBVX基因（HBX）位点突变及其临床意义。方法收集2011年7月至2012年9月门诊与住院符合条件的患者共120例：慢性HBV感染组患者76例，原发性肝细胞癌组患者44例，所有患者血清HBVDNA均在检测上限。选用磁珠吸附法提取血清HBVDNA，巢氏PCR扩增HBX基因，测序，使用Chromas及SeqMan软件比对所得HBX基因序列与GeneBank中的HBV标准株序列，检出其突变位点。组间单因素分析采用独立样本t检验，计数资料组间分析采用f检验，率的比较采用石。检验。结果HBX基因区G1440A、G1467C、G／C1479A、C1485T、C1653T突变位点的发生在两组差异无统计学意义，尸值均〉0．05；肝癌组T1674C位点突变率为29．27％，明显高于慢性HBV感染组的6．67％，x^2=10．827，P=0．001，差异有统计学意义。基本核心启动子区T1753C点突变率和A1762T／G1764A双突变率在肝癌组显著高于慢性HBV感染组，尸值均〈0．05，差异均有统计学意义。T1674C、T1753C、A1762T／G1764A位点突变患者的平均年龄均高于相对应的未突变组，分别为（54．81±13．97）岁对比（46．08±14．14）岁；（55．95±7．99）岁对比（45．37±14．79）岁；（53．18±13．40）岁对比（40．96±12．69）岁，t值分别为2．297、3．117和5．035，P值均〈0．05，差异均有统计学意义。结论HBX基因区T1674C、T1753C及A1762T／G1764A突变在肝癌患者中的发生率高于慢性HBV感染者。T1753C、A1762T／G1764A位点变异可能会抑制HBeAg的水平。Objective To investigate the association of mutations in the hepatitis B virus （HBV） X gene （HBX, encoding the HBx protein） and development of hepatocellular carcinoma （HCC）. Methods Forty-four patients with HBV-related HCC participated in the study, along with 76 patients with chronic HBV infection who assessed as controls. All patients had serum HBV DNA levels that were higher than 103 copies/ml. Extracted HBV DNA was subjected to nested PCR to amplify the HBX gene, followed by direct sequencing. All sequencing data were compared to the consensus HBV sequence to identify mutations. The sequencing data were analyzed by Chromas and SeqMan software. Results Mutations of G1467C, G/C1479A, C1485T and C1653T in the X region were found, but did not show any significant difference in occurrence between the HCC group and the chronic HBV infection group （P 〉 0.05）.The T1674C mutation in the X region, however, occurred more frequently in the HCC group （29.27% vs. 6.67%, P 〈 0.05）. Prevalence of the T1753C mutation and the A1762T/G1764A double mutation in the BCP region was significantly higher in the HCC group than in the chronic HBV infection group （P 〈 0.05） and in the group of patients with hepatitis B e antigen （HBeAg）-negative status compared to the patients with HBeAg-positive status （P 〈 0.05）. Conclusion Incidence of the T1674C mutation in the X region and of the T1753C mutation and the A1762T/G1764A double mutation in the BCP region was higher for patients with HBV-related HCC; the T1753C mutation and the A1762T/G1764A double mutation may inhibit the lbrmation of HBeAg.

关 键 词：肝炎病毒 乙型 突变 乙型肝炎病毒X基因 

分 类 号：R735.7[医药卫生—肿瘤] R512.62[医药卫生—临床医学]