p16影响乙肝病毒相关性肝细胞肝癌的发生

Effect of p16 gene on carcinogenesis of hepatitis B virus related hepatocellular carcinoma

目的 探讨乙肝病毒 (HBV)基因整合和p16基因表达改变及其与肝细胞肝癌发生发展的关系。方法 35例肝癌及癌旁肝组织为标本 ,采用聚合酶链式反应 (PCR)及Southernblot检测HBVX基因整合 ,以单链构象多态性分析确定p16基因突变 ,以RT PCR检测p16mRNA ,以Westernblot检测p16蛋白。结果 肝癌中X基因整合与p16mRNA及蛋白表达相关 (P <0 .0 5 ) ,肝癌及癌旁肝组织中p16蛋白表达缺失率分别为 6 2 .9%和 4 0 .0 % ,差异有显著性 (P <0 .0 5 ) ;癌组织中p16蛋白表达缺失与肝癌分化程度、癌细胞浸润有相关性 (P <0 .0 5 )。结论 X基因整合与p16蛋白缺陷有关 ,p16改变在肝细胞癌变各阶段发挥重要作用 ,并与肝癌的演进和侵袭有关。

Objective To investigate the relation between p16 gene expression and the carcinogenesis and progress of hepatitis B virus(HBV) related hepatocellular carcinoma(HCC). Methods In 35 specimens of HCC tissue and the adjacent liver tissue, the integration of HBV X gene was detected by polymerase chain reaction (PCR) and Southern blot. The point mutation of exon 1α,2 and 3 of p16 gene were detected by PCR single strand conformation polymorphism (SSCP). The expression of p16 mRNA and p16 protein was detected by RT PCR and Western blot. Results The integration of X gene correlated with the expression loss of p16 mRNA and p16 protein in HCC( P <0.05). The expression loss rates of p16 protein in HCC and adjacent tissues were 62.9%(22/35) and 40.0%(14/35) with significant difference ( P <0.05).The expression loss of p16 protein in HCC correlated with the differentiation degrees of HCC and the infiltration of tumor cells( P <0.05). Conclusion The integration of X gene correlates with the expression loss of p16 protein . The alteration of p16 gene, playing an important role in all stages of hepatocarcinogenesis, correlates with the progress and invasion of hepatocellular carcinoma. [