梅尼埃病患者外周单核细胞的基因表达谱分析及药物发现

Gene Expression Profile in Peripheral Blood Mononuclear Cells in Patients with Meniere Disease and Drug Development

目的应用公开数据库寻找可能与梅尼埃病(Meniere's disease,MD)发病机制相关的基因和分子途径,以及筛选MD潜在治疗药物。方法通过Gene Expression Omnibus(GEO)数据库获取GSE109558数据集,筛选MD与正常样本间外周单核细胞的差异表达基因,并进行功能注释、通路分析和蛋白质-蛋白质相互作用PPI(Proteinprotein interaction,PPI)网络构建。最后应用Connectivity map(cMAP)数据库筛选潜在治疗MD的小分子药物。结果差异表达基因显著富集在对病毒的反应、防御反应、趋化、MHC II类蛋白结合等生物过程,以及Influenza A和Herpes simplex infection信号通路。网络分析发现一些核心基因,如CXCL10、IFI44L。筛选出33个治疗MD的候选小分子药物,如赖诺普利、柚皮素等。结论MD可能具有自身炎症性内耳疾病,外周单核细胞中CXCL10、IFI44L、IFI44、XAF1、OAS2、HERC5、EIF2AK2表达水平的升高和POTEE表达水平的降低可能与MD发病机制有关。筛选出的小分子药物,如赖诺普利、柚皮素、伏立诺他等有可能成为MD的治疗或者辅助药物。

Objective To determine genes and molecular pathways associated with pathogenesis of Meniere's disease(MD)using public databases and to identify potential therapeutic drugs for MD.Methods The GSE109558 dataset was acquired from the Gene Expression Omnibus(GEO)database to screen for differentially expressed genes in peripheral monocytes between MD and normal samples,which were then assessed by functional annotation,pathway analysis and protein-protein interaction(PPI).Finally,small molecule drugs potentially beneficial for MD were searched in the Connectivity Map(cMap)database.Results The differentially expressed genes were significantly enriched in biological processes,such as response to virus,defense response,chemotaxis,MHC class II protein binding,and Influenza A and Herpes simplex infection pathways.A few core genes were identified by network analysis,including CXCL10 and IFI44L.Thirty three candidate small molecule drugs,such as lisinopril,naringenin were identified as potentially useful for treating MD.Conclusion MD may be an auto-inflammatory inner ear disease.The up-expression of CXCL10,IFI44L,IFI44,XAF1,OAS2,HERC5 and EIF2AK2 and down-expression of POTEE may be related to the pathogenesis of MD.Small molecule drugs,such as lisinopril,naringenin and vorinostat,may become therapeutic or adjuvant drugs for MD.