特发性癫痫患者外周血差异表达基因筛选及相关生物信息学分析

Identification of differentially expressed genes in peripheral blood of patients with idiopathic epilepsy by bioinformatics analysis

目的通过生物信息学方法分析特发性癫痫患者外周血中关键的差异表达基因(Differentially expressed genes,DEGs)及其生物学功能、细胞定位、参与的信号通路等,为特发性癫痫的发病机制及其防治研究提供新思路。方法从基因表达汇编(Gene expression omnibus,GEO)数据库下载了于2020年1月共享的GEO数据系列GSE143272中的6个未用药的特发性癫痫患者外周血样本,8个丙戊酸钠治疗有效的特发性癫痫患者外周血样本,以及10个健康对照样本的基因芯片数据;其次,在R软件中使用limma包等筛选鉴定出DEGs。然后对所有74个DEGs采用了包括DAVID、STRING及Cytoscape里的Cytohubba应用程序等方法进行了基因功能注释和通路富集分析、PPI网络分析和关键基因分析。结果筛选确定了部分重要的关键DEGs,包括:TREML3P、KCNJ15、ORM1、RNA28S5、ELANE、RETN、ARG1、LCN2、SLPI、HP、PGLYRP1、BPI、DEFA4、TCN1、MPO、MMP9、CTSG、CXCL8、RNASE3、RNASE2、S100A12、DEFA1B、DEFA1、DEFA3、CEACAM8、MS4A3、PTGS2、PI3、CCL3。这些DEGs涉及免疫反应、炎症反应、趋化作用等生物学过程,同时,分子功能集中在过氧化物酶活性、趋化因子活性等,而KEGG通路富集分析显示DEGs主要参与细胞因子-细胞因子受体相互作用、Toll样受体信号通路、趋化因子信号通路等。结论这些重要的关键DEGs可能通过多种信号通路及复杂的机制参与特发性癫痫的发生发展。

Objective To investigate key differentially expressed genes(DEGs) in peripheral blood of idiopathic epilepsy patients, as well as their biological functions, cellular localization, involved signaling pathways, through bioinformatics analysis. So to provide new insights for the pathogenesis and prevention of idiopathic epilepsy.Methods Firstly, we screened and downloaded microarray data including 6 peripheral blood samples of drug-naive patients with idiopathic epilepsy, 8 peripheral blood samples of responders of idiopathic epilepsy treated with Valproate(VPA), and 10 peripheral blood samples of non-responders of idiopathic epilepsy treated with VPA from Gene Expression Omnibus(GEO) data series GSE143272, which Public in January 2020. Secondly, we identified DEGs via the limma package and others in R software. Then we had gotten 74 DEGs, and subsequently conducted gene ontology and pathway enrichment analysis, PPI network analysis and hub gene analysis, using multiple methods containing DAVID, STRING,and Cytohubba in Cytoscape. Results We had identified significant hub DEGs, including TREML3 P, KCNJ15, ORM1,RNA28 S5, ELANE, RETN, ARG1, LCN2, SLPI, HP, PGLYRP1, BPI, DEFA4, TCN1, MPO, MMP9, CTSG, CXCL8,RNASE3, RNASE2, S100 A12, DEFA1 B, DEFA1, DEFA3, CEACAM8, MS4 A3, PTGS2, PI3, CCL3. The biological processes involved in these DEGs include immune response, inflammatory response, chemotaxis, etc. While, the molecular function is focused on peroxidase activity, chemokine activity, etc. Moreover, KEGG pathway enrichment analysis shows that DEGs were mainly involved in cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway and so on. Conclusion These important key DEGs may be involved in the onset and development of idiopathic epilepsy through a variety of signaling pathways and complex mechanisms.