通过生物信息学方法构建系统性红斑狼疮患者的基因表达亚群

Construction of the Gene Expression Subgroups in Patients with Systemic Lupus Erythematosus by Bioinformatics

目的:利用生物信息学方法构建系统性红斑狼疮(SLE)基因表达亚群。方法:从GEO数据库下载GSE121239、GSE65391和GSE154851的微阵列数据集,利用R软件对数据集消除批次效应、聚类共识分组、临床特点分析,使用STRING网站对特异性基因所表达的蛋白质构建蛋白质相互作用(PPI)网络图,筛选枢纽蛋白对应的基因,进行GO功能富集分析和KEGG信号通路分析。结果:共获得1 254例SLE样本、124例健康对照样本。PPI网络分析显示节点最多的蛋白分别为:STAT3、TLR4、BRIX1、TLR2;KEGG分析表明:自然杀伤细胞介导的细胞毒作用、核糖体、线粒体自噬、细胞凋亡、血小板活化、造血细胞谱系、破骨细胞分化、甲型流感等信号通路富集最显著。结论:将SLE患者分成了3个基因亚群,可为该病的诊断、分类及个体化治疗提供潜在的依据。

Objective:To construct the gene expression subgroups in systemic lupus erythematosus by bioinformatics. Methods:The microarray data sets of GSE121239,GSE65391 and GSE154851 were downloaded from GEO database. R software was used to eliminate batch processing effect,cluster consensus grouping and analyze clinical characteristics. PPI network map of proteins expressed by specific genes was constructed by using the STRING website;genes corresponding to pivotal genes were screened,followed by GO analysis and KEGG signal pathway analysis. Results:1 254 SLE samples and healthy control samples were obtained.PPI network analysis showed that the proteins with the wost nodes were STAT3,TLR4,BRIX1 and TLR2. KEGG pathway enrichment analysis showed that differentially expressed genes were significantly enriched in natural killer cell-mediated cytotoxicity,ribosome,mitophagy,apoptosis,platelet activation,hematopoietic cell lineage,osteoclast differentiation,influenza A and other aspects. Conclusion:Systemic lupus erythematosus patients were divided into 3 gene subgroups,which can provide a potential basis for the diagnosis,classification and individualized treatment of the disease.