转录组分析鉴定腰椎椎间盘退行性变中潜在免疫相关生物标志物

Comprehensive transcriptome analysis of potential immune-related biomarkers in lumbar disc degeneration

目的通过转录组分析鉴定腰椎椎间盘退行性变(IDD)中潜在的免疫相关生物标志物,寻找IDD免疫相关的关键靶点。方法从基因表达汇编数据库(GEO)的GSE67567数据集中获得基因表达谱,并筛选差异表达mRNA、长链非编码RNA(lncRNA)和微RNA(miRNA)。使用加权基因共表达网络分析(WGCNA)和基因集富集分析(GSEA)筛选免疫相关模块,并使用Cytoscape构建lncRNA-miRNA-mRNA竞争性内源RNA(ceRNA)网络,通过免疫浸润分析确定相关的免疫细胞,使用Pearson相关分析筛选免疫相关的关键靶点。通过GSEA筛选关键的生物过程和途径。使用GEO的GSE124272数据集验证关键靶基因的表达。结果WGCNA结果表明,蓝绿色模块与免疫力有关。免疫浸润分析显示,CD4幼稚T细胞可能是关键的免疫细胞。Pearson相关分析表明,4个mRNA(UHMK1、ZFP36L2、ZCCHC3、ZBTB20)和1个lncRNA(LINC00641)可能是IDD免疫相关的关键靶点,建立了一个免疫调节相关的ceRNA网络。GSEA结果显示,LINC00641可能通过TGF-β信号通路调节IDD。验证结果表明,这些关键基因在GSE124272数据集中存在差异表达。结论mRNA(UHMK1、ZFP36L2、ZCCHC3、ZBTB20)和lncRNA(LINC00641)是IDD免疫相关的关键靶点。

Objective To identify potential immune-related biomarkers in lumbar disc degeneration(IDD)by comprehensive transcriptome analysis for finding the immune-related key target of IDD.Methods Gene expression profiles were obtained from the GSE67567 dataset of Gene Expression Omnibus database(GEO)and screened for differentially expressed mRNAs,long non-coding RNAs(lncRNAs)and microRNAs(miRNAs).Weighted gene co-expression network analysis(WGCNA)and gene enrichment analysis were used to screen out immune-related modules,and Cytoscape was used to construct lncRNA-miRNA-mRNA competing endogenous RNA(ceRNA)network.The related immune cells were identified through immune infiltration analysis,and the key immune targets were screened by Pearson correlation analysis.The potential pathway of key factors was sceened through gene set enrichment analysis(GSEA).The expression of key target genes was verified in another data set GSE124272.Results According to the result of WGCNA,the turquoise module was related to immunity.After the analysis of immune infiltration,the CD4 naive T cell may be the key immune cell.Pearson correlation analysis showed that 4 mRNAs(UHMK1,ZFP36L2,ZCCHC3 and ZBTB20)and 1 lncRNA(LINC00641)might be the key factors related to immunity in IDD.Then an immunomodulation-related ceRNA network was built.According to the result of GSEA,lncRNA(LINC00641)might regulate IDD through the TGF-βsignaling pathway.The validation results indicated that these key genes exhibited differential expression in the GSE124272 dataset.Conclusion mRNAs(UHMK1,ZFP36L2,ZCCHC3 and ZBTB20)and lncRNA(LINC00641)are the immune-related key target of IDD.