肾透明细胞癌预后相关miRNAs的生物信息学分析

Bioinformatics analysis of prognosis-related miRNAs in clear cell renal cell carcinoma

目的寻找可作为肾透明细胞癌(ccRCC)生物标志物的miRNA,以及ccRCC与正常组织间miRNA差异表达情况。方法利用TCGA数据库下载ccRCC中miRNA表达数据,分析肿瘤与正常组织间差异表达miRNA。使用Kaplan-Meier曲线对患者进行生存分析,筛选出表达情况与临床预后相关的miRNA。通过生物信息学对miRNA的靶基因进行预测,然后运用FunRich软件和ClueGO对靶基因进行GO和KEGG富集分析。结果通过TCGA数据库分析发现,ccRCC较正常组织差异表达miRNA共54个,其中上调33个,下调21个。通过生存分析发现hsa-miR-21和hsa-miR-155与患者预后相关,P≤0.05。进一步通过Perl软件在Targetscan、mi RDB、miRTarBase、miRPath这四个数据库中预测miRNA靶基因并将结果取交集,共发现129个靶基因。GO和KEGG分析结果表明,这些靶基因主要与转录因子活性、信号转导以及FoxO、TNF等信号通路密切相关。结论通过生物信息学分析发现了ccRCC与正常组织的差异表达mi RNA;其中hsa-miR-21和hsa-miR-155与患者总体生存率相关,并通过调控靶基因参与相关的信号通路进而影响ccRCC的发生发展进程,提示hsa-miR-21和hsa-miR-155可能是cc RCC潜在的生物标志物。

Objective To discover miRNAs which can be used as biomarkers of clear cell renal cell carcinoma （ccRCC） as well as ravel differentially expressed miRNAs between ccRCC and normal tissues. Methods The miRNAs expression data of ccRCC was used to analyze differentially expressed miRNAs between tumors and normal tissues according to TCGA database. Survival analysis was performed using Kaplan-Meier curves to screen out miRNAs, which the expression was correlated with clinical prognosis. The target genes of miRNAs were predicted by bioinformatics, then GO and KEGG enrichment analyses of target genes were carried out by using FunRich software and ClueGO software. Results According to TCGA database analysis, there were 54 miRNAs found differentially expressed in ccRCC compared with normal tissues, of which 33 were up-regulated and 21 were down-regulated. Survival analysis found that hsa-miR-21 and hsa- miR-155 were associated with the prognosis of patients （P ≤ 0.05）. A total of 129 target genes were found by using Perl software to predict miRNA target genes in four databases： Targetscan, miRDB, miRTarBase and miRPath. The results of GO and KEGG analysis showed that these target genes were closely related to transcription factor activity, signal transduction, FoxO, TNF and other signaling pathways. Conclusion Differentially expressed miRNAs between ccRCC and normal tissues were found by bioinformatics analysis. Among them, the hsa-miR-21 and hsa-miR-155 may be associated with patient overall survival and influence the development and progression of ccRCC by regulating the target genes involved in the relevant signaling pathways, suggesting that hsa-miR-21 and hsa-miR-155 could be potential biomarkers for ccRCC.