沉默信息调节因子2相关酶1在肝癌中的表达及临床意义

Expression and clinical significance of SIRT1 in hepatocellular carcinoma

目的 探讨沉默信息调节因子2相关酶1（SIRT1）在肝癌中的表达及其临床意义.方法 收集252例乙肝后肝癌病例组织标本及随访资料.通过基因测序分析p53突变情况并通过蛋白印迹法检测肝癌组织中SIRT1和腺苷酸活化蛋白激酶（AMPK）的表达情况.结果 在p53突变型肝癌（n＝54）中,SIRT1活化的比例较野生型p53肝癌高（64.8％比31.8％;P＜0.01）,且活化的SIRT1预示着更高的无复发生存率.多变量分析显示SIRT1是影响无复发生存率的独立因素（OR：0.339,CI：0.160-0.720,P=0.005）.SIRT1活性与AMPK活性显著相关（P =0.007）.结论 在p53突变型肝癌中SIRT1通过AMPK途径表现出抗肿瘤效应.

Objective To investigate the clinical significance of silent mating-type information regulation 2 homologue 1 （SIRT1） in hepatocellular carcinoma （HCC）.Method We analyzed p53 mutation by gene sequencing and activation of SIRT1 and AMP-actived protein kinase （AMPK） using western-blot in 252 patients with hepatitis B virus-positive HCC.Results A higher proportion of tissues with mutant p53 were demonstrated to harbor activated SIRT1 （64.8％ vs 31.8％ ; P ＜ 0.01）.Activated SIRT1 predicted a longer relapse-free survival.On multivariate analysis,activated SIRT1 remained significant （OR：0.339,CI：0.160-0.720,P =0.005）.Analysis of 252 paired specimens revealed a significant correlation between activated SIRT1 and activated AMPK in HCC tissues harboring mutant p53 （P =0.007）.Conclusion SIRT1 exerted anti-carcinogenic effects through the AMPK pathway in HCC in the context of mutant p53.