基于GEO数据库分析支气管肺发育不良发生的关键基因及通路

Bioinformatical analysis of key genes and pathways of bronchopulmonary dysplasia based on GEO database

目的:采用生物信息学方法分析支气管肺发育不良(bronchopulmonary dysplasia,BPD)发生的关键基因和信号通路。方法:在基因表达综合数据库(GEO)中筛选数据集,使用GEO2R工具筛选出BPD与非BPD极早早产儿之间的差异表达基因。使用DAVID数据库进行功能注释和通路分析,使用STRING在线工具完成关键差异表达基因的蛋白质相互作用(PPI)网络构建,通过Cytoscape软件筛选出核心基因,并对其进行可视化处理。结果:差异分析得到表达上调的基因375个,表达下调的基因390个;GO富集分析显示差异表达基因参与细胞对钙离子的反应、RNA聚合酶Ⅱ启动子转录调控、心脏发育等生物过程;KEGG富集分析显示差异表达基因集中于胰高血糖素信号通路、乳腺癌信号通路。通过PPI网络筛选得到10个核心基因,分别为Jun原癌基因(JUN)、Fos原癌基因(FOS)、SWI/SNF染色体重塑复合体亚基4(SMARCA4)、激活转录因子3(ATF3)、早期生长反应蛋白1(EGR1)、Erb-b2受体酪氨酸激酶(ERBB2)、过氧化物酶体增殖物激活受体(PPARA)、FosB原癌基因(FOSB)、核受体亚家族4A组成员1(NR4A1)、胰岛素样生长因子1(IGF1)。结论:JUN、FOS、ATF3、EGR1基因可能在BPD发生发展过程中发挥重要作用。

Objective:To explore the key genes and signal pathways of bronchopulmonary dysplasia(BPD)using bioinformatics.Methods:Data sets were screened in the gene expression omnibus(GEO)database,the GEO2R tool was used to screen the differentially expressed genes between BPD and extremely preterm infants without BPD.Functional annotation and pathway analysis were performed using the DAVID database,protein-protein interaction(PPI)network construction of key DEGs was completed using the STRING online tool.The core genes were screened and visualized by Cytoscape software.Results:A total of 375 genes were up-regulated and 390 genes were down-regulated via differential analysis.GO enrichment analysis showed that differentially expressed genes were involved in cellular response to calcium ions responsiveness,transcriptional regulation of RNA polymeraseⅡpromoter,and heart development.KEGG enrichment analysis showed that differentially expressed genes were concentrated in glucagon signaling pathway and breast cancer signaling pathway.Ten core genes were identified from the constructed PPI network,namely JUN,FOS,SMARCA4,ATF3,EGR1,ERBB2,PPARA,FOSB,NR4A1 and IGF1.Conclusion:JUN,FOS,ATF3 and EGR1 may play an important role in the pathogenesis and development of BPD.