肾透明细胞癌相关基因及通路的筛选及生物信息学分析

Identification of the key genes and pathways of human clear cell renal cell carcinoma by bioinformatics analysis

目的运用生物信息学方法鉴别肾透明细胞癌(ccRCC)发生发展过程中的潜在靶基因及信号通路。方法从GEO网站下载基因芯片GSE53000的数据集,用R软件识别肾透明细胞癌和正常肾组织之间的差异表达基因,并对差异表达基因进行层次聚类分析。然后用DAVID网站对差异基因进行基因本体(Gene ontology)分析和KEGG通路富集分析,最后用STRING网站和Cytoscape软件构建蛋白-蛋白互作(PPI)网络,同时从中筛选出最具有意义的模块,并将其中的基因作为枢纽基因。结果与正常肾组织相比,共计1 175个基因在肾透明细胞癌中差异表达,其中533个基因高表达,642个基因低表达。基因本体分析显示与这些差异基因相关度最高的10个生物学过程分别是细胞粘附、白细胞迁移以及炎症反应等,KEGG分析结果显示最显著的10条信号通路包括补体和凝血级联通路、细胞粘附分子通路以及细胞因子-细胞因子受体互作通路。从PPI网络中共挑选出20个枢纽基因,其中有12个与炎症反应过程相关。结论被鉴别出来的12个基因很有可能在肾透明细胞癌的发病过程中发挥重要的作用,可能在将来被用作人类肾透明细胞癌的治疗靶点和/或诊断标志物。

Objective To identify the potential target genes and signal pathways in the development of renal clear cell carcinoma(ccRCC)by bioinformatics analysis.Methods The data of GSE53000 were downloaded from the GEO website.The differential expression genes(DEGs)between ccRCC and normal renal tissue were identified with R Software.The clustering analysis and functional enrichment analysis of these DEGs were then performed,followed by protein-protein interaction(PPI)network and pathway relation network.Meanwhile,the most significant module based on PPI network was selected,and the genes in the module were identified as hub genes.Results Compared with normal renal tissue,ccRCC had a total of 1 175 genes which were differentially expressed.Among them,533 were up-regulated and 642 were down-regulated.Genomic analysis showed that the 10 biological processes with the highest correlation with these differential genes were cell adhesion,leukocyte migration and inflammatory response.KEGG analysis showed that the 10 most significant signal pathways included complement and coagulation cascade,adhesion molecule pathway and cytokine-cytokine receptor interaction pathway.Altogether 20 throttle genes were selected from the PPI network,12 of which were associated with the inflammatory response process.ConclusionThe identified 12 genes are likely to play an important role in the pathogenesis of ccRCC and may be used as a therapeutic target and/or diagnostic marker for ccRCC in the future.