基于WGCNA联合免疫浸润探讨斑秃发病机制及靶向中药预测分析

The analysis of the pathogenesis of alopecia areata and targeted traditional Chinese herb prediction based on combined immune infiltration with WGCNA

目的应用WGCNA联合免疫浸润方法,分析斑秃发病的核心差异基因及免疫浸润情况并预测斑秃治疗的有效中药。方法下载基因芯片数据集GSE68801,通过表达差异和模块分析筛选差异基因,在CTD和STRING平台对差异基因进行富集分析及PPI网络构建,应用Cytoscape筛选PPI网络中的核心基因并通过ROC曲线预测诊断效能,并以GSE45512数据集对核心基因进行验证。采用CIBERSORT分析AA组织中免疫细胞浸润情况,通过spearman筛选与免疫浸润相关的核心基因,并通过CoremineMedical数据库预测有效中药。结果筛出差异基因255个,主要参与头发周期、细胞因子与细胞因子受体相互作用、趋化因子信号通路、Th1和Th2细胞分化等。PPI网络中具有诊断效能的核心基因主要有BMP2、CCL5、CXCL10、CXCL9、IL10RA、CD2、CD3D、CD8A、ITGAL,免疫浸润主要为T cells gamma delta、Macrophages M1和Macrophages M2的浸润程度明显增多,而Mast cells resting浸润程度下降,相关核心基因为BMP2、CD8A、CXCL10、IL10RA、ITGAL等,预测的有效中药主要为枸杞子、当归、丹参、人参、红花、甘草等。结论通过生物信息学方法获得与AA免疫浸润高度相关的核心基因,并预测有效中药,为深入探索AA发病机制及靶向治疗提供理论依据。

Objective To analyze the core differential genes,enrichment process,and immune infiltration of alopecia areata(AA),and to predict the effective traditional Chinese herb for the treatment of AA.Methods GSE68801 dataset was downloaded,and differential genes were screened by expression difference and module analysis.Differential genes were enriched by CTD and PPI network was constructed by STRING platform.Core genes in the PPI network were screened by Cytoscape and their diagnostic efficacy was predicted by ROC curves.The GSE45512 dataset was used to validate.CIBERSORT was used to analyze the infiltration of immune cells in AA tissues,and the core genes related to immune infiltration were screened by Spearman.Effective traditional Chinese herbs were predicted by core memedical database.Results A total of 255 differentially expressed genes were identified,which were mainly involved in hair cycle,cytokine-cytokine receptor interaction,chemokine signaling pathway,and Th1 and Th2 cell differentiation.The core genes of PPI were BMP2,CCL5,CXCL10,CXCL9,IL10RA,CD2,CD3D,CD8A,ITGAL.The infiltration of T cells gamma delta,Macrophages M1 and Macrophages M2 increased significantly,while Mast cells resting decreased.The related core genes were BMP2,CD8A,CXCL10,IL10RA,ITGAL.The predicted effective Chinese herbs included wolfberry,Chinese angelica,salvia miltiorrhiza,ginseng,safflower,and licorice.Conclusion The core genes related to the immune infiltration of AA are obtained by bioinformatics methods,and the effective Chinese herbal medicines are predicted,which can provide theoretical basis for further exploring the pathogenesis and targeted therapy of AA.