基于GEO数据集筛选良性前列腺增生的关键基因及信号通路

Screening of key genes and associated signaling pathways in benign prostatic hyperplasia based on GEO database

目的通过生物信息学方法筛选良性前列腺增生(BPH)的关键基因和相关通路,探究BPH发生、发展可能的病理、生理机制。方法利用基因表达汇编(GEO)数据库下载BPH与正常前列腺组织的两个芯片数据(GSE7307与GSE119195),通过Rstudio软件对数据集进行差异基因(DEGs)筛选及京都基因与基因组百科全书(KEGG)分析及可视化;运用Cytoscape软件中的ClueGO插件进行基因本体论(GO)富集分析与可视化。利用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,在Cytoscape中可视化,并通过Cytoscape中的cytoHubba插件得到关键基因。通过NetworkAnalyst预测调控关键基因的转录因子和miRNA。结果本分析共得到36个上调DEGs,45个下调DEGs。GO分析发现DEGs主要富集于干细胞负性增殖调控、乙醇初步代谢、维生素效应等生物学过程,KEGG主要富集于Hippo信号通路、PPAR信号通路、肾素分泌等信号通路;最终得到CCL2、LPL、VCAN、IGF1、WNT2这5个关键基因。结论本研究通过生物信息学方法筛选获得可能参与BPH发生、发展的关键基因及其相关通路,为阐明BPH的发病机制提供了一定的理论基础。

Objective To screen the key genes and signaling pathways associated with BPH occurrence and development utilizing bioinformatics methods,and to explore the possible pathophysiologic mechanism of BPH.Methods The datasets(GSE7307 and GSE119195)which comparing BPH with normal prostate tissue were downloaded from GEO database,then the Rstudio software was used to seek for the differential expression genes(DEGs)in the BPH and normal prostate tissue,and complete the KEGG analysis and visualization.The GO analysis and visualization were performed by ClueGO in the Cytoscape software.The PPI network was obtained from the String database and visualized in Cytoscape software,then key genes were selected by cyto Hubba in Cytoscape software.Finally,forecasted transcription factors and miRNA which might to regulate the key genes were forecasted though NetworkAnalyst.Results After screening DEGs in GSE7307 and GSE119195,36 co-upregulated genes and 45 co-downregulated genes were selected.The GO analysis showed that DEGs were mainly enriched in negative regulation of stem cell proliferation,primary alcohol metabolic process,response to vitamin and other biological processes,while KEGG were mainly enriched in Hippo signaling pathway,Renin secretion,PPAR signaling pathway and others.In the end,CCL2,LPL,VCAN,IGF1,WNT2 were chosen to be the key genes.Conclusions This research obtained the key genes and associated signaling pathways that might be related to pathophysiologic mechanism of BPH,providing a certain theoretical basis to elucidate the pathogenesis of BPH.