特应性皮炎局部皮损发生的关键基因筛选

Screening Key Genes of Local Skin Lesions of Atopic Dermatitis

目的筛选特应性皮炎(AD)局部皮损发生的关键基因及预测潜在的治疗药物。方法从GEO数据库中获得GSE153007基因芯片数据,运用R语言进行数据矫正、差异表达基因的筛选、GO功能富集和KEGG通路富集分析,并通过STRING在线数据库进行蛋白互作分析,用Cytoscape软件中的插件MCODE进行子网络模块分析,筛选出特应性皮炎局部皮损发生的关键基因,最后利用Connectivity Map预测减轻特应性皮炎局部皮损的潜在小分子化合物。结果本研究共筛选出100个差异表达基因和8个关键基因LCE3A、LCE3D、PI3、SPRR1A、SPRR1B、SPRR2D、SPRR2G和SPRR2E。GO分析共富集164个功能,包括抗菌体液反应、分泌颗粒腔、RAGE受体结合等;KEGG分析共富集6个通路,差异表达基因与IL-17信号通路最相关。预测出奥利司他、多沙唑嗪、PU-H71、AZD-7762、TUL-XXI039和RS-504393小分子化合物可作为减轻特应性皮炎局部皮损的潜在药物。结论LCE3A、LCE3D、PI3、SPRR1A、SPRR1B、SPRR2D、SPRR2G和SPRR2E可能是特应性皮炎局部皮损发生、发展相关的关键基因,预测的6个小分子化合物可为后续药物研究提供理论参考。

Objective To screen key genes in local skin lesions of atopic dermatitis(AD),as well as to predict potential therapeutic drugs.Methods With GSE153007 gene chip data obtained from GEO database,data correction,differentially expressed genes(DEGs)screening,GO functional enrichment analysis and KEGG pathway enrichment analysis were conducted by using R language.The protein interaction network was analyzed with STRING online database,and subnetwork module was analyzed with Cytoscape plugin MCODE.After the key genes of atopic dermatitis were screened out,the Connectivity Map was used to predict potential small molecule compounds for treating local skin lesions of AD.Results A total of 100 differentially expressed genes and eight key genes(LCE3 A,LCE3 D,PI3,SPRR1A,SPRR1B,SPRR2D,SPRR2G and SPRR2E)were screened in this study.With GO analysis,164 functions were enriched,including humoral response to bacteria,secretory granule,RAGE binding,etc.;with KEGG analysis,six pathways were enriched,and differentially expressed genes have the strongest correlation with IL-17 signaling pathway.Orlistat,doxazosin,PU-H71,AZD-7762,TUL-XXI039,and RS-504393 small molecule compounds were predicted to be used as potential drugs for reducing the local skin lesions of AD.Conclusion LCE3A,LCE3D,PI3,SPRR1A,SPRR1B,SPRR2D,SPRR2G and SPRR2E may be key genes relating to the occurrence and development of the local skin lesions of AD.The six small molecule compounds are predicted to offer positive clinical outcome that can provide theoretical references for subsequent drug research.