乙型肝炎病毒X蛋白氨基端变异与肝癌发生的相关性分析  

Correlation of the mutations in N terminal of hepatitis B virus X protein with tumorigenesis of hepatocellular carcinoma

作　　者：白鑫[1,2] 朱宇[1] 金晏[2] 蔡小锦[2] 郭霞[2] 钱耕荪[2] 陈陶阳[3,4] 张菁 王金兵[3,4] 屠红[1,2] 

机构地区：[1]上海交通大学肿瘤研究所癌基因及相关基因国家重点实验室,上海200032 [2]上海交通大学肿瘤研究所诊断室,上海200032 [3]启东肝癌防治研究所 [4]启东肿瘤医院病因室,启东226200 [5]上海市大华医院中西医结合肝病科,上海200237

出　　处：《肿瘤》2010年第5期433-437,共5页Tumor

基　　金：“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项项目(编号:2008ZX10002-015)

摘　　要：目的:探讨乙型肝炎病毒X蛋白(hepatitis B virus X protein,HBx)氨基端1～90位氨基酸(amino acid,AA)变异与肝细胞癌发生之间的关系。方法:采用PCR扩增产物直接测序的方法,对48例肝癌组织、159例肝癌和144例慢性肝炎患者血清中HBVX基因进行序列分析。通过病例-对照研究HBx变异与肝癌发生之间的关系。结果:肝癌组织中HBx氨基端变异集中于1～49 AA区域,突变率为4.1%;50～90 AA为保守区,突变率仅为0.46%。血清检测结果显示,HBx氨基端突变在肝癌患者中的发生率显著高于肝炎患者(2.2%vs1.8%,P<0.05);HBx第36位Ala/Thr/Pro→Ser的突变,在肝癌患者中的发生率为10.1%,显著高于肝炎患者中的2.1%[P<0.01,比数比(odds ratio,OR)=5.259,95%可信区间为1.499～18.444)]。A/T/P36S突变仅发生于C基因型病毒。结论:HBx氨基端突变的累积可能与肝癌的发生有关。HBx A/T/P36S突变能增加C基因型HBV感染者发生肝癌的危险度。Objective：To explore the relationship between mutations at 1-90 amino acid（AA） in N terminal of hepatitis B virus X protein（HBx） and the occurrence of hepatocellular carcinoma（HCC）.Methods：The HBV X gene sequences were analyzed by using PCR direct sequencing method in 48 HCC tissues and serum samples of 159 HCC patients and 144 chronic hepatitis patients.A case-control study was used to analyze the relationship between HBx mutation and tumorigenesis of HCC.Results：The N terminal mutation of HBx isolated from HCC tissues was located at 1-49 AA,while 50-90 AA were conserved regions.The average mutation rates in hypervariable and conserved regions were 4.1% and 0.46%,respectively.The serum detection results showed that frequency of HBx N terminal mutation was higher in HCC patients than in non-HCC control patients（2.2% vs 1.8%,P〈0.05）.A mutation of Ala/Thr/Pro to Ser at codon 36 was significantly increased in HCC patients compared with hepatitis patients [10.1% vs 2.1%,P〈0.01;odds ratio（OR）=5.259,95% confidence interval of 1.499-18.444].A/T/P36S mutation occurred only in type C virus.Conclusion：Accumulation of the N terminal mutations in HBx was related with tumorigenesis of hepatocellular carcinoma.HBx A/T/P36S mutation increased the risk of developing HCC in patients infected with type C HBV.

关 键 词：癌 肝细胞 肝炎 乙型 慢性 突变 乙型肝炎病毒X蛋白 

分 类 号：R735.7[医药卫生—肿瘤]