肝癌ADRA1A基因甲基化和mRNA表达及其临床意义  

Methylation and mRNA expression of ADRA1A gene in hepatocellular carcinoma and its clinical significance

作　　者：王磊[1] 王文耀[1] 李彬[1] 高飞[1] 张少君[1] WANG Lei;WANG Wenyao;LI Bin;GAO Fei;ZHANG Shaojun(Department of General Surgery,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院普外科一科,石家庄050000

出　　处：《临床肿瘤学杂志》2024年第5期441-445,共5页Chinese Clinical Oncology

摘　　要：目的探讨肝细胞癌(HCC)中肾上腺素能受体α1A(ADRA1A)基因甲基化状态和mRNA表达,并分析其临床意义。方法从癌症基因组图谱(TCGA)数据库中查询ADRA1A信息,使用cBioPortal、Gene Expression Omnibus和GEPIA在线公共数据集分析数据,通过GEPIA数据集中的“Kaplan-Meier-plotter”分析ADRA1A相对表达对总生存期(OS)的影响。收集2017年3月至2018年11月间在河北医科大学第二医院就诊的90例HCC患者,采用实时荧光定量PCR(qPCR)测定HCC组织和癌旁组织中ADRA1A表达,采用甲基化特异性聚合酶链反应(MSP)检测ADRA1A甲基化状态。采用受试者工作特征(ROC)曲线评估ADRA1A基因表达诊断HCC的效能。Kaplan-Meier法绘制生存曲线;Cox比例风险回归模型分析影响HCC患者预后的因素。结果TCGA数据库分析得到ADRA1A是HCC中肾上腺素能受体中的甲基化基因,且ADRA1A高表达的患者生存显著改善。HCC组织中ADRA1A相对表达水平显著低于癌旁组织[0.63(0.31,1.07)vs.0.96(0.85,1.17),P<0.001]。ROC曲线结果显示,ADRA1A基因表达水平区分HCC和癌旁组织的曲线下面积(AUC)为0.702(0.619~0.785)。HCC组织中ADRA1A甲基化率显著高于癌旁组织(47.78%vs.23.33%,P=0.001)。ADRA1A甲基化患者HCC组织的ADRA1A表达显著低于ADRA1A非甲基化患者[0.39(0.16,0.72)vs.0.93(0.55,1.55),P<0.001]。ADRA1A甲基化仅与UICC分期有关(P<0.05)。Kaplan-Meier生存分析结果显示,ADRA1A非甲基化患者的中位OS未达,显著高于ADRA1A甲基化患者的13.0个月(6.5~19.4个月),差异有统计学意义(P<0.05)。多因素Cox回归分析结果显示,ADRA1A甲基化和甲胎蛋白(AFP)是影响HCC患者OS的独立因素(P<0.05)。结论ADRA1A基因高甲基化可能是HCC有效的诊断和预后预测标志物。Objective To investigate the methylation status and mRNA expression of adrenergic receptor alpha 1A(ADRA1A)gene in hepatocellular carcinoma(HCC),and analyze its clinical significance.Methods ADRA1A information was queried from TCGA dataset,and the data were analyzed using cBioPortal,Gene Expression Omnibus and GEPIA online public data.Kaplan-Meier-plotter in the GEPIA dataset was used to analyze the effect of ADRA1A relative expression on overall survival(OS).A total of 90 HCC patients admitted to the Second Hospital of Hebei Medical University from March 2017 to November 2018 were collected.Real-time quantitative fluorescent PCR(qPCR)was used to determine the expression of ADRA1A in HCC tissues and adjacent tissues,and methylation-specific polymerase chain reaction(MSP)was used to detect the methylation status of ADRA1A.The efficacy of ADRA1A gene expression in the diagnosis of HCC was evaluated by receiver operating characteristic curve(ROC).The survival curves was drawed by Kaplan-Meier.Cox proportional regression model was used to analyze the prognostic factors of HCC patients.Results The TCGA database analysis showed that ADRA1A was a methylated gene in the adrenergic receptor in HCC,and the survival of patients with high expression of ADRA1A was significantly improved.The relative expression level of ADRA1A in HCC tissues was significantly lower than that in paracancer tissues[0.63(0.31,1.07)vs.0.96(0.85,1.17),P<0.001].ROC curve results showed that the area under curve(AUC)of ADRA1A gene expression level differentiating HCC and paracancer tissues was 0.702(0.619-0.785).The methylation rate of ADRA1A in HCC tissues was significantly higher than that in paracancer tissues(47.78%vs.23.33%,P=0.001).The expression of ADRA1A in HCC tissues was significantly lower in patients with ADRA1A methylation than that in patients with ADRA1A non-methylation[0.39(0.16,0.72)vs.0.93(0.55,1.55),P<0.001].The methylation of ADRA1A was only associated with UICC stage(P<0.05).Kaplan-Meier analysis showed that the median OS of ADRA

关 键 词：肝细胞癌 ADRA1A 预后 肾上腺素能受体 

分 类 号：R735.7[医药卫生—肿瘤]