基于生物信息学方法筛选系统性红斑狼疮疾病进展中与先天免疫细胞相关的关键基因

Bioinformatics-based approach to screen key genes associated with innate immune cells in the development of systemic lupus erythematosus

目的:通过生物信息学方法识别系统性红斑狼疮(SLE)疾病进展中与先天免疫细胞相关的的关键基因。方法:在GEO数据库中下载了GSE50772、GSE81622、GSE99967数据集的表达谱,并对其进行整合。应用CIBERSORT工具对疾病进行免疫细胞组成和丰度的分析,利用加权基因共表达网络分析(WGCNA)来构建基因共表达网络,对关键模块进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析,并与差异表达基因相结合,识别先天免疫反应相关的关键基因。结果:通过加权共表达网络分析(WGCNA),确定了与SLE相关的13个模块。其中绿色模块与中性粒细胞显著相关,棕褐色模块与NK细胞显著相关。在绿色模块中筛选出15个枢纽基因,棕褐色模块中筛选出8个枢纽基因。结合差异表达基因进一步筛选出2个hub基因,分别为CXCL1和MME。使用GSE122459数据集对其进行验证,在SLE患者中,CXCL1与MME基因的表达升高,AUC值分别为0.86和0.81,且其表达均与中性粒细胞的比例显著相关。结论:CXCL1和MME基因可能在SLE发展过程中在先天免疫细胞中发挥重要作用。

Objective:To identify key genes associated with innate immune cells in the development of systemic lupus erythematosus(SLE)by bioinformatics approaches.Methods:The expression profiles of three datasets,GSE50772,GSE81622,and GSE99967,were downloaded from the GEO database and integrated.The CIBERSORT was applied to analyze immune cell composition and abundance for disease,and weighted gene co-expression network analysis(WGCNA)was used to construct gene co-expression networks,and key modules were analyzed for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment,and combined with differentially expressed genes to identify key genes associated with the innate immune response.Results:By WGCNA analysis,13 modules associated with SLE were identified.Among them,the green module was significantly associated with neutrophils and the tan module was significantly associated with NK cells.Fifteen hub genes were screened in the green module,and 8 hub genes were screened in the tan module.Two hub genes,CXCL1 and MME,were further screened in combination with differentially expressed genes.They were validated using the GSE122459 dataset,and the expression of CXCL1 and MME genes were elevated in SLE patients with AUC values of 0.86 and 0.81,respectively,and their expressions were both significantly correlated with the proportion of neutrophils.Conclusion:CXCL1 and MME genes may play important roles in innate immune cells during the development of SLE.