基于SurvivalMeth数据库分析NMUR1在乳腺癌中的甲基化状态及其对预后的作用

Methylation of NMUR1 and Its Prognostic Role in Breast Invasive Carcinoma:Analysis Based on the Data-mining of SurvivalMeth

为研究神经介素U受体1(NMUR1)在乳腺癌(BRCA)中的甲基化状态及其对预后的作用,通过UALCAN数据库中癌症基因组图谱(TCGA)数据分析NMUR1在组织中的表达水平,并利用人类蛋白质图谱(HPA)数据库对其进行进一步验证;采用SurvivalMeth数据库分析NMUR1在BRCA中的甲基化状态,并通过比例风险(COX)回归分析、Kaplan-Meier生存分析研究NMUR1甲基化状态与BRCA患者预后的相关性。共纳入分析UALCAN数据库中TCGA-BRCA肿瘤组织样本1097例和正常乳腺组织样本114例,结果发现,NMUR1在BRCA组织中的表达显著下调(P<0.001)。甲基化分析显示,NMUR1在BRCA组织中的cg00143376、cg01649597、cg02204630、cg10042319、cg16297948、cg17207690、cg18250832、cg18877969、cg19077400、cg21424120、cg26913833位点上的甲基化水平有显著差异(P<0.001)。Kaplan-Meier生存分析结果表明,NMUR1在BRCA组织中胞嘧啶-磷酸-鸟嘌呤(CpG)岛甲基化高风险组(n=320)患者的生存率显著低于低风险组(n=461)[风险比(HR)=2.140300,95%CI(1.3054,3.5091),P=0.001]。与低风险组相比,高风险组在cg18877969(P=0.015)、cg16297948(P=0.028)、cg19077400(P=0.011)、cg26913833(P=0.035)位点的CpG岛甲基化水平较高。NMUR1在BRCA组织中呈高甲基化状态,且NMUR1 CpG岛甲基化与BRCA患者的预后相关,这为NMUR1作为BRCA预后和(或)治疗的新靶点提供了依据。

To investigate the methylation of NMUR1(neuromedin U receptor 1)in breast invasive cancer(BRCA)and its prognostic role in prognosis,the UALCAN database was used to analyze the expression level of NMUR1 in TCGA(the cancer genome atlas)-BRCA tissues,and The Human Protein Atlas database was used for verification.SurvivalMeth database was used to analyze the methylation levels of NMUR1 in BRCA,and COX regression analysis and Kaplan-Meier survival analysis were conducted to study the correlation between the methylation levels of NMUR1 and the prognosis of BRCA patients.In the UALCAN database,1097 TCGA breast cancer tissue and 114 normal breast tissue were included,and NMUR1 expression was significantly down-regulated in breast tissue compared with normal breast tissue(P<0.001).The methylation analysis showed that NMUR1 had significant differences in the methylation levels of cg00143376,cg01649597,cg02204630,cg10042319,cg16297948,cg17207690,cg18250832,cg18877969,cg19077400,cg21424120 and cg26913833 in BRCA tissues(P<0.001).Kaplan-Meier survival analysis showed that the survival rate of NMUR1 patients in the high-risk CpG island meth-ylation group(n=320)in BRCA tissues was significantly lower than that in the low-risk group(n=461)[HR=2.1403,95%CI(1.3054,3.5091),P=0.001].Compared with the low-risk group,the CpG island methylation level was higher in the high-risk group at cg18877969(P=0.015),cg16297948(P=0.028),cg19077400(P=0.011),and cg26913833(P=0.035).NMUR1 is hypermethylated in BRCA tissues,and CpG island methylation of NMUR1 is related to the prognosis of BRCA patients,that providing evidence for NMUR1 as a new target for BRCA prognosis and/or treatment.