ADH家族在肝细胞癌中的表达及其临床意义  

The expression and clinical significance of ADHs in hepatocellular carcinoma

作　　者：帕成周 邬善敏[1] PA Cheng‐zhou;WU Shan‐min(Department of Hepatobiliary Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院肝胆外科,湖北武汉430060

出　　处：《海南医学院学报》2021年第17期1307-1311,1318,共6页Journal of Hainan Medical University

基　　金：武汉市科技攻关项目(201161038342-02)。

摘　　要：目的:探究ADH家族在肝细胞癌(HCC)中的表达及其在预后评价方面的作用。方法:本研究临床资料来源于TCGA数据库,利用MetabolicgEneRApidVisualizer数据库、TCGA数据库对ADH家族在正常肝组织和HCC的mRNA表达情况进行差异分析,筛选出差异表达的ADH家族进行Kaplan‐Meier生存分析;采用Cox分析选择可能影响HCC预后的因素及验证HCC患者的独立危险因素。通过GeneMAMIA、STRING在基因层面和蛋白表达水平上探索ADH家族成员间的相互作用,并采用DAVID生物信息学资源对ADH家族进行功能富集分析。结果:在HCC中ADH1A、ADH1B、ADH1C、ADH4、ADH7低表达;ADH1A、ADH1B、ADH1C、ADH4低表达组生存率较差,可能与HCC患者不良预后相关;单因素Cox回归分析表明ADH1A、ADH1C、ADH4表达水平、肿瘤临床分期、T分期、M分期与患者总体生存率密切相关;多因素Cox回归分析则进一步提示ADH1A、ADH1C、ADH4低表达是影响HCC患者预后的独立危险因素。ADH1A‐ADH1B、ADH1B‐ADH1C、ADH1A‐ADH1C基因之间存在通路,ADH家族与酯酶D、乙醛脱氢酶联系密切。ADH家族主要参与乙醇氧化及视黄醇代谢等生物过程,主要通过糖酵解/糖异生、化学致癌作用、细胞色素P450对药物的代谢等通路发挥生物学作用。结论:ADH1A、ADH1C、ADH4可能是HCC患者预后评判的有效生物标志物,为ADH家族在HCC的实际应用提供参考价值。Objective:To explore the expression and prognostic significance of ADHs in hepatocellular carcinoma(HCC).Methods:The clinical data in this study were retrieved from The Cancer Genome Atlas(TCGA).The expression of ADHs was differentially analyzed in normal liver tissues and HCC by using the Metabolic gEne RApid Visualizer and the TCGA database,and the differentially expressed ADHs were selected for Kaplan‐Meier survival analysis.Cox analysis was performed to select factors that may influence the prognosis of HCC and to verify independent risk factors for HCC patients.The interaction among ADHs was explored at the gene level and protein expression level through GeneMAMIA and STRING,and the functional enrichment analysis of ADH family was carried out by using DAVID bioinformatics resources.Results:The expression levels of ADH1A,ADH1B,ADH1C,ADH4 and ADH7 in HCC were low.Patients with low expression level of ADH1A,ADH1B,ADH1C and ADH4 had poor survival rates,which may be related to the poor prognosis of HCC.Univariate Cox regression analysis showed that the expression levels of ADH1A,ADH1C and ADH4,as well as the clinical stage,T stage and M stage of the tumor were closely related to the overall survival rate of the patients.Multivariate Cox regression analysis further suggested that the low expression of ADH1A,ADH1C and ADH4 were independent risk factors affecting the prognosis of HCC patients.There was a pathway between ADH1A‐ADH1B,ADH1B‐ADH1C and ADH1A‐ADH1C,and ADHs were closely related to esterase D and aldehyde dehydrogenase.The ADHs were mainly involved in biological processes such as ethanol oxidation and retinol metabolism,and played a biological role in glycolysis/gluconeogenesis,chemical carcinogenesis and metabolism of xenobiotics by cytochrome P450.Conclusion:ADH1A,ADH1C and ADH4 may be biomarkers for the prognosis of HCC,providing reference value for the practical application of ADHs in HCC.

关 键 词：肝细胞癌 乙醇脱氢酶 TCGA 

分 类 号：R735.7[医药卫生—肿瘤]