Screening of Hub Genes Associated with Lupus Nephritis by Integrated Bioinformatic Analysis

Min Wang, Xingruo Zeng, Ning Zhu, Bin Wu
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Abstract

Lupus Nephritis (LN) is one of the commonest complications of systemic lupus erythematosus which is characterized by autoimmune and tissue destruction. Elucidating the process in detail would be of great significance for clinical practice, however, the molecular mechanism underlying LN is not clear. In the study, GSE112943 and GSE81622 were retrieved from Gene Expression Omnibus database (GEO), and the differentially expressed genes (DEGs) were identified by GEO2R. Among these DEGs, 42 genes were up-regulated, and 7 genes were down-regulated. The functions and signaling pathways of these DEGs were analyzed systematically, and protein-protein interaction (PPI) networks of these DEGs were established through the search tool for the retrieval of interacting genes (STRING) database. 10 hub genes (IFI44, RSAD2, IFI44L, IFI27, MX1, IFIT3, IFIT1, IFI6, OAS3 and IFIT2) were screened out by the plug-in CytoHubba in Cytoscape. Expression level, diagnosis value as well as correlation with glomerular filtration rate (GFR) expression of these hub genes for LN patients were investigated in GEO datasets and Nephroseq v5 online platform. The results showed that eight of these hub genes were found highly expressed in LN tissues and significantly related to the diagnosis (AUC>0.7; p<0.05). In addition, these hub genes were negatively related to the GFR level of LN patients. In conclusion, the hub genes and pathways that were related to the development of LN were screened out, which could provide a new insight for the future molecularly targeted therapy and diagnostic evaluation. Key words: Lupus Nephritis (LN), Bioinformatics, Differentially Expressed Genes (DEGs), Hub Genes, diagnosis.
综合生物信息学分析筛选狼疮性肾炎相关枢纽基因
狼疮肾炎(LN)是系统性红斑狼疮最常见的并发症之一,其特点是自身免疫和组织破坏。详细阐明这一过程对临床实践具有重要意义,然而,LN的分子机制尚不清楚。本研究从基因表达综合数据库(Gene Expression Omnibus database, GEO)中检索GSE112943和GSE81622,通过GEO2R对其差异表达基因(differential Expression genes, deg)进行鉴定。其中42个基因表达上调,7个基因表达下调。系统分析了这些基因的功能和信号通路,并通过相互作用基因检索工具(STRING)数据库建立了这些基因的蛋白-蛋白相互作用(PPI)网络。通过Cytoscape插件CytoHubba筛选出10个枢纽基因(IFI44、RSAD2、IFI44L、IFI27、MX1、IFIT3、IFIT1、IFI6、OAS3和IFIT2)。在GEO数据集和Nephroseq v5在线平台上研究这些中心基因在LN患者中的表达水平、诊断价值以及与肾小球滤过率(GFR)表达的相关性。结果显示,其中8个枢纽基因在LN组织中高表达,且与LN的诊断有显著相关性(AUC>0.7;p < 0.05)。此外,这些枢纽基因与LN患者GFR水平呈负相关。综上所述,筛选出与LN发展相关的枢纽基因和通路,为未来的分子靶向治疗和诊断评价提供新的思路。关键词:狼疮性肾炎,生物信息学,差异表达基因,中枢基因,诊断
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