肝癌患者乙型肝炎病毒基因变异的检测  

Investigation on mutations of hepatitis B virus gene in the patients with hepatocellular carcinoma

作　　者：白敬羽[1] 周国平[1] 罗立波[1] 颜建华[1] 潘永军[1] 时静[1] 王永忠[1] 杭双熊[1] 陈敏[1] 

机构地区：[1]江苏省常州市第三人民医院,213001

出　　处：《中华传染病杂志》2007年第10期617-620,共4页Chinese Journal of Infectious Diseases

基　　金：江苏省社会发展资金资助项目(BS200311)

摘　　要：目的了解肝癌患者HBV基因变异、机体免疫功能异常及肿瘤抑制基因P16蛋白失活的情况。方法运用基因芯片和核苷酸序列分析技术,对114份我院住院患者血清中HBV DNA (前C区1814、1896、BCP区1762、1764位)进行分析,流式细胞荧光染色检测患者外周血WBC中P16蛋白,流式细胞仪检测T淋巴细胞亚群,ELISA法检测IFN-γ、IL-4水平。结果慢性乙型肝炎组(41份)、乙型肝炎肝硬化组(37份)、肝癌组(36份)血清中的HBV总突变率为58.5%、75.6%和88.8%,肝组织中肝硬化、肝癌分别为75.0%和100%;慢性乙型肝炎、乙型肝炎肝硬化、肝癌组患者外周血WBC中P16蛋白阳性率分别为(43.09±8.08)%、(30.54±10.61)%和(16.29±6.86)%,正常人为(76.57±6.07)%;肝癌患者CD3^+、CD4^+、CD8^+T淋巴细胞绝对数均明显低于健康对照组(t_1′=8.83、t_2′=6.59、t_3′=9.84,P<0.05);肝癌患者IFN-γ、IL-4水平明显低于健康者(t_1′= 6.67、t_2′=3.82,P<0.05)。结论肝癌患者中HBV基因变异普遍存在,机体免疫功能低下,外周血WBC中P16蛋白表达明显低。Objective To detect hepatitis B virus（HBV） genomic mutations, immune dysfunc tion and inactivation of tumor suppressor gene P16 and their correlation with hepatocellular carcinoma. Methods HP, V gene mutation was detected by microarray and sequencing technology in serum of 114 cases. P16 proteins in peripheral blood leukocytes with fluorescence dyeing and T lymphocyte subsets were detected with flow cytometry. Serum interleukin-4 （IL-4） and interferon gamma（IFN-γ） were detected by enzyme-linked immunosorbent assay（ELISA）. Results The gene mutation rate of HBV in serum was 58.5%, 75.6% and 88.8% in 41 chronic hepatitis（CHB） and 37 liver cirrhosis （LC） and 36 hepatocellular carcinoma（HCC） cases, respectively, while the mutation rate of HBV in liver tissues was separately 75.0% and 100% in LC and HCC cases. The positive rate of P16 protein expressed in peripheral blood leukocytes of blood donors and patients with CHB, LC and HCC was （76.57± 6.07）%, （43.09±8.08）%, （30.54± 10.61）% and （16.29±6.86）%, respectively. The absolute numbers of CD3^＋ , CD4^＋ and CD8^＋ T lymphocytes in patients with HCC were lower than those of normal adults（t＇1= 8.83, t＇2=6.59, t＇3= 9.84, P 〈 0.05）. The serum levels of IFN-γ and IL-4 in patients with HCC were lower than those of normal adults（t＇1 = 6.67, t＇2 = 3.82, P〈0.05）. Conclusion HBV gene mutations are common, immune function and the expression of P16 are significantly inhibited in the patients with hepatocellular carcinoma.

关 键 词：肝炎病毒 乙型 基因 病毒 变异(遗传学) 蛋白P16 基因 P16 免疫 细胞 癌 肝细胞 

分 类 号：R735.7[医药卫生—肿瘤]