Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis.

Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis.
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通过综合生物信息学分析识别系统性红斑狼疮的关键生物标志物和免疫浸润

DOI:
10.1186/s12967-020-02698-x
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发表时间:
2021-01-19
影响因子:
7.4
通讯作者:
You Y
You Y
中科院分区:
医学2区
文献类型:
--
作者:
Zhao X;Zhang L;Wang J;Zhang M;Song Z;Ni B;You Y

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系统性红斑狼疮(SLE)是一种以破坏性全身脏器受累为特征的多系统慢性炎症性疾病,可导致功能减退、发病率和死亡率增加。以往的研究表明,系统性红斑狼疮的特点是自身免疫、炎症过程和组织破坏。一些重病患者可能发展为狼疮和肾炎。然而,SLE的病因和潜在的分子事件需要进一步解决。从基因表达总表(GEO)数据库下载GSE144390、GSE4588、GSE50772和GSE81622的表达谱,以获得SLE与健康样本之间的差异表达基因(Deg)。通过Metasscape等在线分析方法,对DEGS的基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径进行了丰富。用GENEMANIA软件构建蛋白质-蛋白质相互作用(PPI)网络。为了进一步了解HUB基因的功能,我们进行了基因集浓缩分析(GSEA),利用加权基因共表达网络分析(WGCNA)来构建基因共表达网络,并确定了最重要的模块和HUB基因。CiberSort工具有助于分析疾病的免疫细胞渗透模式。通过受试者工作特性(ROC)分析,探讨DEGS在SLE诊断中的价值。共筛选出6个DEG(IFI27、IFI44、IFI44L、IFI6、EPSTI1和OAS1),生物学功能分析确定了SLE的关键相关通路、基因模块和共表达网络。IFI27可能与SLE的发生密切相关。我们发现单核细胞的浸润增多,而静息的NK细胞浸润较少,可能与SLE的发生有关。IFI27可能与SLE的发病机制密切相关,是SLE发生发展的一个新的候选分子标志物。此外,免疫细胞浸润在SLE的进展中起着重要作用。
Systemic lupus erythematosus (SLE) is a multisystemic, chronic inflammatory disease characterized by destructive systemic organ involvement, which could cause the decreased functional capacity, increased morbidity and mortality. Previous studies show that SLE is characterized by autoimmune, inflammatory processes, and tissue destruction. Some seriously-ill patients could develop into lupus nephritis. However, the cause and underlying molecular events of SLE needs to be further resolved. The expression profiles of GSE144390, GSE4588, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between SLE and healthy samples. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by metascape etc. online analyses. The protein–protein interaction (PPI) networks of the DEGs were constructed by GENEMANIA software. We performed Gene Set Enrichment Analysis (GSEA) to further understand the functions of the hub gene, Weighted gene co‐expression network analysis (WGCNA) would be utilized to build a gene co‐expression network, and the most significant module and hub genes was identified. CIBERSORT tools have facilitated the analysis of immune cell infiltration patterns of diseases. The receiver operating characteristic (ROC) analyses were conducted to explore the value of DEGs for SLE diagnosis. In total, 6 DEGs (IFI27, IFI44, IFI44L, IFI6, EPSTI1 and OAS1) were screened, Biological functions analysis identified key related pathways, gene modules and co‐expression networks in SLE. IFI27 may be closely correlated with the occurrence of SLE. We found that an increased infiltration of moncytes, while NK cells resting infiltrated less may be related to the occurrence of SLE. IFI27 may be closely related pathogenesis of SLE, and represents a new candidate molecular marker of the occurrence and progression of SLE. Moreover immune cell infiltration plays important role in the progession of SLE.
DOI: 10.1093/bioinformatics/btr260
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DOI: 10.1136/lupus-2014-000080
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发表时间: 2017-11-01
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