基于TCGA数据库分析DARS2在膀胱癌中的临床意义

Clinical significance and molecular mechanism of DARS2 in bladder cancer based on TCGA database

目的 基于癌症基因组图谱(TCGA)数据库,分析线粒体天冬氨酰-tRNA合成酶2(DARS2)基因在膀胱癌患者和正常组织中的表达差异,研究其与患者临床特征、预后相关性及参与膀胱癌的调节信号通路。方法 从TCGA数据库下载膀胱癌相关的表达资料和临床特征资料,使用R.4.0.3软件和Strawberry Perl 5.32.0.1提取膀胱癌组织和正常组织中DARS2的表达量数据,利用Mann-Whitney U检验比较两组间的表达差异。将DARS2基因表达量按照中位值分为高表达组和低表达组,采用卡方检验分析表达量与临床特征的关系。利用单因素和多因素cox回归分析对预后意义进行评估,使用Kaplan-Meier法进行生存分析并采用在线数据库验证,利用基因富集分析(GSEA)预测DARS2在膀胱癌中参与的信号通路。结果 膀胱癌组DARS2的表达量明显高于正常组,差异有统计学意义(P<0.05),DARS2在膀胱癌患者中的表达与Stage分期(P<0.05)和T分期(P<0.05)有关。DARS2(HR=2.08,95%CI:1.34~3.25,P<0.05)可作为膀胱癌的独立预后因素。DARS2高表达组的总生存率显著低于低表达组,差异有统计学意义(P<0.05),与OncoLnc在线数据库验证结果一致。GSEA富集分析表明DARS2主要参与细胞周期、RNA降解、核苷酸切除修复、错配修复、P53信号通路、DNA复制。结论 DARS2在膀胱癌患者中高表达,与Stage分期和T分期有关,可以作为导致膀胱癌预后不良的独立危险因子,并通过多种信号途径促进膀胱癌的发生发展。

Objective To analyze the expression of aspartyl-tRNA synthetase2,mitochondrial(DARS2)in bladder cancer patients and normal tissues based on The Cancer Genome Atlas(TCGA)database,to investigate the correlation between DARS2 and clinical characteristics,prognosis and to predict signal pathway in bladder cancer. Method The expression data and clinical characteristics of bladder cancer were downloaded from TCGA database. The expression data of DARS2 in bladder cancer tissues and normal tissues were extracted by R.4.0.3 software and Strawberry Perl 5.32.0.1,and the expression difference between the two groups were compared by Mann-Whitney U test. DARS2 expression was divided into the high expression group and the low expression group according to the median. Chi-square test was used to analyze the relationship between expression and clinical characteristics. Univariate and multivariate cox regression analysis were used to evaluate the prognostic significance. Kaplan-Meier was used for survival analysis and online database verification. Gene enrichment analysis(GSEA)was used to predict the signal pathway of DARS2 in bladder cancer.Result The expression of DARS2 in the bladder cancer group was significantly higher than that in the normal control group(P<0.05). The expression of DARS2 in bladder cancer patients was related to stage and T stage.DARS2(HR=2.08,95%CI:1.34~3.25,P<0.05)can be used as an independent prognostic factor for bladder cancer. The overall survival rate of the group with high expression of DARS2 was lower than that of the group with low expression of DARS2(P<0.05),which was consistent with the results of Onco Lnc online database.GSEA enrichment analysis showed that DARS2 was mainly involved in cell cycle,RNA degradation,nucleotide excision repair,mismatch repair,p53 signal pathway and DNA replication. Conclusion DARS2 is highly expressed in patients with bladder cancer,which is related to stage and T stage. It can be used as an independent risk factor for poor prognosis of bladder cancer and promote the occurrence and development of bladder cancer through various signaling pathways.