乙型肝炎病毒基因变异、p16蛋白失活与肝癌的相关性研究

Investigation of mutation of hepatitis B virus DNA gence and out of control p16 tumor suppressor genes protein with hepatocellullar carcinoma(HCC).

目的探讨乙型肝炎病毒(HBV)基因变异及肿瘤抑制基因p16蛋白失活与肝癌发生的关系。方法用基因芯片和核苷酸序列分析技术对114例HBV感染者(观察组)血清和43份肝组织标本中HBV DNA(前C区1814、1896、BCP区1762、1764位)进行分析,用流式细胞荧光染色法检测观察组和20例正常献血者(正常对照组)外周血白细胞中p16蛋白表达。结果观察组慢性重症乙型肝炎、肝硬化、肝癌患者血清HBV基因总突变率显著高于慢性乙型肝炎患者(P<0.01),肝硬化、肝癌肝组织HBV基因总突变率显著高于正常组织;正常对照组外周血白细胞中p16蛋白阳性率显著低于慢性乙型肝炎、肝硬化、肝癌患者,肝硬化、肝癌患者阳性率显著高于慢性乙型肝炎患者。结论HBV变异可能是肝癌发生的始动因子,而p16蛋白失活是肝癌发生的重要因素。

[ Objective ] To detect hepatitis B virus DNA gence mutation, and to detect the correlation of deactivation of p16 with hepatocellullar carcinoma. [ Methods] HBV DNA mutation was detected using microarray and sequenceing technologies, p16 in the peripheral blood leukocyte was detected using flow cytometry.. [ Results] The mutation of hepatitis B virus DNA in serum was 55.8% ,75.6% ,88.8% in chronic hepatitis（CHB） and liver cirrhosis（LC） and HCC cases, Theirs in liver tissue was 75.0% and 100% in LC and HCC cases. The positive rate of p16 expressed in the peripheral blood leukocytes of donate blood person and CHB and LC and HCC was 76. 57 ~6.07%,43.09 ~8.08%,30. 54 ~ 10.61%, 16.29 ~ 6.86%. [ Conclusion ] HBV DNA mutation is initiation factor of HCC. The cellurlar immunity dysfunction was pathology foundation. The musing P16 proteion was the importment factor of HCC.