基于TCGA分析肝细胞癌组织miR-5003-3p表达变化及其与患者预后的关系

Expression changes of miR-5003-3p in hepatocellular carcinoma tissues and its relationship with the prognosis of patients based on TCGA data

目的分析肝细胞癌(HCC)组织中miR-5003-3p的表达变化,探讨其与患者临床参数、预后的关系。方法利用癌症基因图谱(TCGA)数据库下载375例份HCC组织样本和50例份癌旁组织样本的微小RNA(miRNAs)测序数据,并收集375例患者的临床资料。采用生物信息学方法观察miR-5003-3p在HCC组织中的表达变化,分析其与患者临床参数的相关性。通过绘制受试者工作特征(ROC)曲线评估miR-5003-3p在HCC预后判断中的价值,运用COX比例风险回归模型分析miR-5003-3p对患者预后的影响。结果HCC组织(375例份)和癌旁组织(50例份)中miR-5003-3p相对表达量分别为0.432±0.429、0.160±0.233,二者比较P<0.01;配对的HCC组织和癌旁组织(各49例份)中miR-5003-3p相对表达量分别为0.547±0.491、0.163±0.233,二者比较P<0.01。375例HCC患者根据miR-5003-3p表达中位数分为高表达组187例、低表达组187例。miR-5003-3p表达与T分期(OR=1.955)、病理分期(OR=1.763)和肿瘤状态(OR=1.659)有显著相关性(P均<0.05)。高表达组10年总生存期(OS)、疾病特异生存期(DSS)和无进展间隔期(PFI)均显著低于低表达组(P均<0.01)。ROC曲线结果显示,miR-5003-3p预测HCC患者1、3、5年OS的曲线下面积(AUC)分别为0.655、0.627、0.586,预测HCC患者1、3、5年DSS的AUC分别为0.720、0.640、0.582,预测HCC患者1、3、5年PFI的AUC分别为0.581、0.614、0.644。miR-5003-3p表达升高(HR=1.788,P=0.017)是影响HCC患者OS的独立危险因素。结论HCC组织miR-5003-3p表达升高,miR-5003-3p异常高表达是HCC患者预后不良的独立危险因素,并对患者预后具有良好的预测价值。

Objective To analyze the expression changes of miR-5003-3p in the hepatocellular carcinoma(HCC)tissues,and to investigate its relationship with clinical characteristics as well as prognosis of patients.Methods The miRNA sequencing data and clinical information of 375 HCC tissues and 50 paired normal tissues were downloaded from The Cancer Genome Atlas(TCGA)database,and the clinical data from 375 patients were collected.Then the expression changes of miR-5003-3p in the HCC tissues and its correlation with clinical characteristics was analyzed by using bioinfor⁃matic methods.The diagnostic value of miR-5003-3p for prognosis prediction of HCC patients was evaluated by drawing the receiver operating characteristic(ROC)curve.The effect of miR-5003-3p expression on the prognosis of HCC patients was analyzed by using COX proportional hazards regression model.Results The relative expression levels of miR-5003-3p in the HCC(375 cases)and adjacent tissues(50 cases)were 0.432±0.429 and 0.160±0.233,respectively,with statistically significant difference(P<0.01).The relative expression levels of miR-5003-3p in the matched HCC tissues(49 cases)and adjacent tissues(49 cases)were 0.547±0.491 and 0.163±0.233,respectively,with statistically sig⁃nificant difference(P<0.01).Then,HCC patients(375 cases)were divided into the high expression group of 187 cases and low expression group of 187 cases based on the median expression of miR-5003-3p.The expression of miR-5003-3p was significantly related to T stage(OR=1.955,P=0.006),pathological stage(OR=1.763,P=0.023),and tumor status (OR=1. 659,P=0. 019). The 10-year overall survival(OS),disease specific survival(DSS)and progression-free interval (PFI)of patients were significantly lower in the high expression group than in the low expression group(all P<0. 01). ROC curve analysis based on miR-5003-3p expression revealed that the area under the curve(AUC)of the 1-,3-,and 5- year OS prediction was 0. 655,0. 627,and 0. 586,respectively. The AUC of the 1-,3-,and 5-year DSS prediction was 0. 720,0. 640,and 0. 582,respectively. The AUC of the 1- ,3- ,and 5-year PFI prediction was 0. 581,0. 614,and 0. 644,respectively. COX regression analysis showed that high expression of miR-5003-3p was an independent risk factor for OS of HCC patients(HR=1. 788,P=0. 0176). Conclusion The miR-5003-3p expression increases in HCC tissues, and the abnormally high miR-5003-3p expression in HCC tissues is an independent risk factor for poor prognosis of HCC patients,which exhibits good predictive value for the prognosis of HCC patients.