多组学联合分析神经胶质瘤中SOX4表达差异及临床意义

Analysis of the Expression Level and Clinical Significance of SOX4 in Glioma Based on Multi-omics

目的通过多组学分析探究SOX4(SRY-Box Transcription Factor 4)在恶性胶质瘤(GBM)和低级别胶质瘤(LGG)中的表达差异及临床意义。方法从TCGA和GTEx数据库中下载25种肿瘤表达谱数据。采用R软件分析GBM和LGG组织中SOX4 mRNA表达差异。通过ScTIME Portal数据库分析胶质瘤单细胞中SOX4 mRNA表达情况。ROC曲线评估SOX4对GBM和LGG的诊断价值。通过基因富集分析(GO、KEGG和GSEA)筛选SOX4共表达基因功能。STRING数据库构建共表达基因相互作用网络(PPI)。利用cBioPortal数据库分析SOX4基因突变率。运用MethSurv数据库分析SOX4基因甲基化水平及其与预后的关系。通过ssGSEA分析SOX4表达与免疫细胞浸润相关性。结果SOX4 mRNA在GBM和LGG中高表达。SOX4在GBM(AUC=0.978)和LGG(AUC=0.985)中诊断价值较高。基因富集发现37个SOX4共表达基因与外泌体及囊腔、神经脊分化、炎症反应、有丝分裂和DNA修复有关。SOX4在GBM和LGG中突变率分别为0.4%和1.5%。SOX4基因Cg22274825、Cg08625851、Cg00792966和Cg23780597位点DNA甲基化水平与GBM和LGG预后密切相关。SOX4与GBM和LGG中肿瘤免疫细胞Th2、Tgd、Tcm、TFH、T helper cells、pDC等密切相关。结论SOX4是潜在的GBM和LGG诊断和预后生物标志物,有望成为神经胶质瘤的治疗靶点。

Objective To investigate the differential expression and clinical significance of SOX4 in glioma(GBM and LGG)by multi-omics analysis.Methods The gene expression profiles of 25 cancers were downloaded from TCGA and GTEx databases.The differential expression of SOX4 in GBM and LGG were analyzed by R software.ScTIME Portal databases was used to reveal SOX4 expression in single cell.Receiver operating characteristic(ROC)analysis was employed to assess diagnostic values of SOX4 mRNA in GBM and LGG.Gene enrichment analysis,including GO,KEGG and GSEA,were used to predict the function of SOX4 co-expression genes.Protein interaction network were constructed by STRING database.SOX4 gene mutations were analyzed by the cBioPortal databases,and DNA methylation levels of SOX4 and its relation with prognosis were performed by MethSurv database.Immune cell infiltration analysis associated with SOX4 were assessed by ssGSEA and Spearman.Results SOX4 mRNA was highly expressed in GBM and LGG tissues.SOX4 expression had diagnostic value in both GBM(AUC=0.978)and LGG(AUC=0.985).Functional enrichment analysis showed that 37 SOX4 co-expression genes were associated with exosomes,cavities,neuroridge differentiation,inflammatory response,mitosis and DNA reparation.In GBM and LGG,SOX4 mutation rates were 0.4%and 1.5%,respectively.DNA methylation levels of Cg22274825,Cg08625851,Cg00792966 and Cg23780597 in SOX4 genes were strongly associated with GBM and LGG prognosis.SOX4 mRNA levels was closely related to tumor immune cellsin GBM and LGG,including Th2,Tgd,Tcm,TFH,T helper cells,pDCs,et al.Conclusion SOX4 is a potential biomarker for the diagnosis and prognosis of GBM and LGG,and it will be anunderlying target for therapeutic interventions.