落叶型天疱疮发病的关键基因和通路:基于生物信息学方法  

Key genes and pathways involved in the pathogenesis of pemphigus foliaceus:Based on bioinformatic studies

作　　者：朱雅倩 李欣辉 贾子悦 陈永锋[1,2] ZHU Yaqian;LI Xinhui;JIA Ziyue;CHEN Yongfeng(Guangdong Medical College,College of Dermatology,Anhui Medical University;Dermatology Hospital,Southern Medical University,Guangzhou 510091,China)

机构地区：[1]安徽医科大学广东皮肤病临床学院 [2]南方医科大学皮肤病医院,广东广州510091

出　　处：《皮肤性病诊疗学杂志》2023年第2期100-106,共7页Journal of Diagnosis and Therapy on Dermato-venereology

基　　金：安徽省教育厅科学研究项目(YJS20210325)。

摘　　要：目的利用生物信息学方法鉴定参与落叶型天疱疮(PF)发病的关键基因和通路,进一步了解PF发病机制。方法从GEO数据库中获取PF患者外周血CD4^(+)T细胞的基因芯片数据集GSE53873,整合Limma差异分析、基因功能和通路富集分析、蛋白质-蛋白质相互作用网络分析等多种生物信息学方法,确定与PF相关的关键基因及通路。结果共鉴定121个显著上调基因和48个显著下调基因。PF患者的差异基因涉及到T细胞分化、T细胞活化、白细胞分化与代谢等多个方面。最终确定CXCL10及OAS1是PF发病的关键基因。受试者工作特征曲线(ROC)结果提示CXCL10(AUC=0.86)及OAS1(AUC=0.86)对PF具有较高的诊断效能。基因功能和通路富集分析提示CXCL10主要与TOLL样受体信号通路、COVID-19感染、细胞因子相互作用相关,而OSA1主要与病毒感染、Ⅰ型干扰素信号通路等相关。结论CXCL10及OAS1为与PF相关的关键基因,T细胞分化与活化、白细胞分化与代谢等通路与天疱疮发病机制相关。Objective Using bioinformatic technique to identify key genes and pathways involved in the pathogenesis of pemphigus foliaceus(PF),in order to elucidate the pathogenesis of PF.Methods Gene microarray dataset GSE53873 of peripheral blood CD4^(+)T cells from PF patients was obtained from Gene Expression Omnibus database,and various bioinformatics methods such as Limma difference analysis,gene function and pathway enrichment analysis,and proteinprotein interaction network analysis were integrated to determine the key genes and pathways associated with PF.Results A total of 121 significantly upregulated genes and 48 significantly downregulated genes were identified in PF patients compared with healthy controls.The differentially expressed genes in PF patients were involved in multiple functions such as T cell differentiation,T cell activation,leukocyte differentiation and metabolism.CXCL10 and OAS1 were identified as key genes in the pathogenesis of PF.Receiver operating characteristic(ROC)results suggested that CXCL10(AUC=0.86)and OAS1(AUC=0.86)had high diagnostic efficacy for PF.Gene function and pathway enrichment analysis indicated that CXCL10 was mainly associated with TOLL-like receptor signaling pathway,COVID-19 infection,and cytokine interaction,while OSA1 was mainly associated with viral infection and type I interferon signaling pathway.Conclusions CXCL10 and OAS1 are the key genes associated with PF.The pathogenesis of pemphigus is associated with pathways such as T cell differentiation and activation,leukocyte differentiation and metabolism.

关 键 词：落叶型天疱疮 基因组测序 CXCL10 OAS1 CD4^(+)T细胞 

分 类 号：R758.66[医药卫生—皮肤病学与性病学]