基于CIBERSORT算法分析皮肌炎免疫浸润机制与中药治疗靶点预测  

Analysis of immune infiltration mechanism of dermatomyositis and prediction of therapeutic targets of traditional Chinese medicine based on CIBERSORT algorithm

作　　者：王朴 胡敏 潘素跃 黄巧 陈东宇 樊文龙 杨晓雨 王红心 何玉清 WANG Pu;HU Min;PAN Suyue;HUANG Qiao;CHEN Dongyu;FAN Wenlong;YANG Xiaoyu;WANG Hongxin;HE Yuqing(Department of Epidemiology and Health Statistics,School of Public Health,Guangdong Medical University,Institute of Medical Systems Biology,Guangdong Medical University,Dongguan 523808,China;Dongguan Liaobu Hospital,Dongguan 523400,China)

机构地区：[1]广东医科大学公共卫生学院流行病与卫生统计学系,广东医科大学医学系统生物学研究所,东莞523808 [2]东莞市寮步医院,东莞523400

出　　处：《中国免疫学杂志》2025年第4期783-791,I0001,共10页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(81773312);广东省“扬帆计划引进紧缺拔尖”人才项目(201433005);东莞市社会发展科技重点项目(20221800906082)。

摘　　要：目的:基于生物信息学方法分析皮肌炎基因芯片并利用CIBERSORT反卷积算法探究皮肌炎关键基因的免疫浸润机制,预测其中药治疗靶点。方法:在GEO数据库检索皮肌炎基因芯片,筛选出差异共表达基因并进行分析;运用R软件包对差异共表达基因进行GO分析、KEGG分析、构建蛋白质互作网络(PPI);验证关键基因的表达水平;利用CIBERSORT反卷积法分析免疫细胞浸润机制;通过医学本体信息检索平台Coremine medical数据库,筛选皮肌炎的中药治疗靶点并进行归纳分析。结果:共筛选出196个差异共表达基因。GO富集分析显示这些差异共表达基因主要富集在病毒的防御反应、血液微粒、双链RNA结合、多肽抗原结合力等方面;KEGG富集分析显示其主要涉及RIG-Ⅰ样受体信号通路、Toll样受体信号通路等以及与皮肌炎发病相关的信号通路。本研究最终得到了STAT1、ISG15、IRF7、IRF94个皮肌炎关键基因。CIBERSORT算法分析结果显示,M1巨噬细胞、M2巨噬细胞、CD8+T细胞平均占比最高,是免疫浸润最明显的3种细胞;活化的自然杀伤细胞与活化的树突状细胞之间存在较为明显的正相关性,静息的肥大细胞与活化的肥大细胞之间存在较为明显的负相关性。通过Coremine medical数据库筛选出鱼脑石等相关中药治疗靶点;归经分析显示这些中药主要集中在肝经、肺经、脾经;功效分析则主要集中在清热、解毒、活血化瘀以及止咳化痰等方面。结论:本研究通过生物信息学方法得到了STAT1、ISG15、IRF7、IRF94个皮肌炎关键基因;通过CIBERSORT算法表明其与免疫浸润细胞之间存在较强相关性;筛选出了鱼脑石等具有治疗潜力的中药靶点,为研究皮肌炎的发病机制和治疗方法提供了新的参考。Objective:To analyze the gene chip related to dermatomyositis based on bioinformatics,to explore the immune infiltration mechanism of key genes in dermatomyositis by CIBERSORT deconvolution algorithm,and to predict the therapeutic targets of dermatomyositis by network pharmacology.Methods:The gene microarray of dermatomyositis was searched in GEO database,and the differentially coexpressed genes were screened and analyzed.The differentially coexpressed genes were analyzed by GO analysis,KEGG analysis,protein interaction network construction(PPI)by R software package.Verify the expression levels of key genes,and the correlation of immune cell infiltration was analyzed by CIBERSORT deconvolution method.Through the medical ontology information retrieval platform Coremine medical database,the traditional Chinese medicine treatment targets of dermatomyositis were screened and summarized.Results:A total of 196 differentially expressed genes were screened.GO enrichment analysis showed that these differentially expressed genes were mainly concentrated in defense response to virus,blood particles,double-stranded RNA binding,polypeptide antigen binding,and so on.KEGG enrichment analysis showed that it was enriched in RIG-Ⅰ-like receptor signal pathway,Toll-like receptor signal pathway and other signal pathways related to the pathogenesis of dermatomyositis.Finally,four key genes of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained.Through CIBERSORT algorithm,M1 macrophages,M2 macrophages and CD8+T cells were the three kinds of cells with the highest average proportion and the most obvious immune infiltration,and there was a significant positive correlation between activated natural killer cells and activated dendritic cells,while there was a significant negative correlation between resting mast cells and activated mast cells.The therapeutic targets of traditional Chinese medicine such as fish brain stone were predicted based on Coremine medical database;through channel analysis,it could be found that these traditio

关 键 词：皮肌炎 CIBERSORT 生物信息学 免疫浸润 中药靶点 

分 类 号：R593.26[医药卫生—内科学]