摘要
目的利用生物信息学方法筛选狼疮性肾炎(LN)的关键表达基因,寻找诊断LN的潜在生物标志物,探讨LN的发病机制。方法从高通量基因表达(GEO)数据库下载慢性肾脏病相关的GSE99339数据集,用WGCNA方法筛选与LN相关的核心模块。获取CSE32591数据集,对32例LN患者和14例正常对照的肾小球基因表达谱进行差异分析,将差异基因与WGCNA筛选的LN核心模块基因取交集。使用DAVID在线工具对交集基因进行GO功能注释和KEGG通路富集分析,构建蛋白质相互作用网络(PPI),并使用Cytoscape软件筛选关键基因。基于验证集GSE112943的基因表达数据,绘制关键基因的箱线图和ROC曲线,评估其诊断效能。结果黄绿色模块(102个基因)与LN强相关(r=0.85,P<0.01)。GSE32591数据集的差异表达基因有361个,与黄绿色模块基因取交集得到53个共有基因。LN相关基因主要富集于抗病毒反应、固有免疫、丙型肝炎和流感病毒A等生物学过程和信号通路。PPI网络分析显示,排名前5的关键基因分别为IFIT3、MX1、OAS1、RSAD2和OAS3。IFIT3、MXI、OAS1和RSAD2基因在LN组和正常对照组间存在显著差异(P<0.05),ROC曲线分析表明这4个基因预测LN的ROC曲线下面积值均大于0.8,具有较高的诊断效能。结论IFIT3、MXI、OAS1和RSAD2可能是LN的关键表达基因,有望成为LN的潜在诊断生物标志物和治疗靶点。
Objective To identify the key differentially expressed genes in the patients with lupus nephritis(LN)using bioinformatics methods and discover potential diagnostic biomarkers of LN for exploring the pathogenic mechanisms of LN.Methods The GSE99339 dataset related to chronic kidney disease was obtained from the Gene Expression Omnibus(GEO)database.Weighted gene co-expression network analysis(WGCNA)was performed to identify the core modules highly correlated with LN.The differentially expressed genes(DEGs)between the two groups(32 LN patients and 14 healthy controls)from GSE32591 dataset were identified using Limma package.The intersection of DEGs and the LN-related module genes was obtained.The Gene Ontology(GO)function annotation and Kyoto Encyclopedia of Genes and Genomes(KECG)pathway enrichment analyses of intersection genes were conducted using DAVID online tool to construct protein-protein interaction(PPI)network,and the key genes were screened using Cytoscape software.Boxplots and receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic efficiency of the key genes based on the the gene expression data of CSE112943 validation dataset.Results The greenyellow module(102 genes)was strongly correlated with LN(r=0.85,P<0.01).A total of 361 DEGs were identified from GSE32591 dataset,among which 53 genes were found to intersect with the green-yellow module genes.The LN-related genes were mainly enriched in the biological processes and pathways which related to antiviral response,innate immunity,hepatitis C,and influenza A virus.The top five key genes in the PPI network were IFIT3,MX1,OAS1,RSAD2,and OAS3.The expression levels of IFIT3,MXI,OASI and RSAD2 in LN were significantly different from control groups(P<0.05).ROC curve analysis showed that the AUC values for the four genes in predicting LN were all greater than 0.8,indicating high diagnostic efficiency.Conclusion IFIT3,MXI,OAS and RSAD2 may be the key differentially expressed genes in LN and may be potential diagnostic biomarkers and therapeutic targets for LN.
作者
张莉
龚政
马钧
罗亚维
蒋丽琼
ZHANG Li;GONG Zheng;MA Jun;LUO Yawei;IANG Liqiong(Department of Medical Laboratory,Nanjing Medical Unversity Affliated Suzhou Hospital,Suzhou 215001,Jiangsu,China;Department of Nephrology,Nanjing Medical Unversity Affliated Suzhou Hospital,Suzhou 215001,Jiangsu,China)
出处
《临床检验杂志》
2025年第2期136-143,共8页
Chinese Journal of Clinical Laboratory Science
基金
苏州市智慧+重大疾病生物标志物研究与转化重点实验室项目(SZS2024029)
苏州市肾脏病学重点学科项目(Szxk201807)。
关键词
高通量基因表达
狼疮性肾炎
加权基因共表达网络分析
富集分析
high-throughput gene expression
lupus nephritis
weighted gene co-expression network analysis
enrichment analysis
作者简介
张莉,1991年生,女,主管技师,硕士,主要从事临床检验工作;通讯作者:蒋丽琼,副主任医师,E-mail:98qiong2008@163.com。
