基于WGCNA研究激素性股骨头坏死相关核心靶点

Analysis of related core targets of hormonal femoral head necrosis based on WGCNA

目的:利用加权基因共表达网络(WGCNA)探索激素性股骨头坏死(SANFH)的生物学治疗靶点。方法:从GEO数据库中下载GSE123568芯片数据,标准化后进行差异分析和WGCNA,以|Log2FC|>1和P<0.05作为差异基因的筛选条件,并结合WGCNA挖掘与SANFH相关性最高的共表达模块,找到共有的交集基因,分析GO和KEGG的富集情况,了解交集基因的生物学功能,将交集基因导入String数据库中构建蛋白质相互作用网络(PPI)图,利用Cytoscape3.7.2软件中的cytoHubba寻找Hub基因,对Hub进行功能富集分析及受试者工作特征曲线(ROC曲线)诊断验证,利用GeneMANIA数据库构建Hub基因之间的网络互作图。结果:从GEO数据库中下载样本40例,包括正常组10例和SANFH组30例,通过差异分析获得了384个满足条件的基因,经WGCNA方法得到4个共表达模块,从中筛选出相关性高的模块,结合差异基因共得到225个交集基因,交集基因的功能富集结果显示,主要在红细胞和骨髓细胞的发育、分化及稳态上富集明显;通过Cytoscape3.7.2软件分析最终得到4个关键基因:GATA1、SLC4A1、EPB42和DMTN,关键基因的富集结果和交集基因的富集结果一致,ROC曲线提示4个基因具有很好的诊断价值。结论:本研究分析得到4个与SANFH具有显著相关性的关键基因,这些基因表达的降低可能促进SANFH的发生和发展,可作为诊断和治疗的潜在靶标。

Objective:The weighted gene co-expression network(WGCNA)was used to explore the biological therapeutic targets of steroid-induced femoral head necrosis.Methods:The GSE123568 chip data were downloaded from the GEO database,and subjected to difference analysis and WGCNA analysis after standardization.With|Log2 FC|>1 and P<0.05 as the screening conditions of differential genes,and in combination with WGCNA,the co-expression modules with the highest correlation with hormonal femoral head necrosis were mined to find out the common intersection genes.The enrichment and the biological functions of the intersection genes were analyzed and understood by GO and KEGG.The intersecting genes were imported into String database to construct protein-protein interaction network diagram.CytoHubba in Cytoscape3.7.2 software was used to find the Hub gene,and the functional enrichment analysis and Receiver operating characteristic curve(ROC)diagnosis verification of Hub were performed.The network diagram between Hub genes was constructed using GeneMANIA database.Results:Forty samples were downloaded from the GEO database,including 10 normal samples and 30 SANFH samples.A total of 384 genes meeting the conditions were obtained through difference analysis,and four co-expression modules were obtained through WGCNA analysis,from which the modules with high correlation were screened out,and a total of 225 intersecting genes were obtained by combining with the differential genes.The functional enrichment results of the intersecting genes showed that the enrichment was significant mainly in the development,differentiation and steady state of red blood cells and bone marrow cells.Through the analysiswith Cytoscape3.7.2 software,four key genes were finally obtained:GATA1,SLC4 A1,EPB42 and DMTN.The enrichment results of key genes were consistent with those of intersecting genes,and ROCcurve indicated that the four genes had good diagnostic value.Conclusion:Through analysis in this study,we have obtained four key genes that had significant correlation with steroid-induced femoral head necrosis.The reduced expression of these genes may promote the occurrence and development of steroid-induced femoral head necrosis,which might be potential targets for diagnosis and treatment.