通过生物信息学分析鉴定子痫前期发病机制中的狼疮相关基因

IF 2.3 Q3 BIOCHEMICAL RESEARCH METHODS Bioinformatics and Biology Insights Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI:10.1177/11779322241271558
Qianwen Dai, Mengtao Li, Xinping Tian, Yijun Song, Jiuliang Zhao
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引用次数: 0

摘要

子痫前期(PE)是一种严重的妊娠并发症,在系统性红斑狼疮(SLE)患者中更为常见。虽然这些病症的确切病因还不完全清楚,但免疫系统在其中扮演了关键角色。为了研究系统性红斑狼疮与 PE 之间的联系,我们分析了可能导致 PE 发生的系统性红斑狼疮相关基因。我们从 NCBI GEO 数据库中收集了 9 个微阵列数据集,并使用 Limma 来识别差异表达基因(DEGs)。此外,我们还利用加权基因共表达网络分析(WGCNA)确定了系统性红斑狼疮的枢纽基因,并利用 Cibersort 分析了免疫浸润。通过构建蛋白-蛋白相互作用(PPI)网络和使用 CytoHubba,我们确定了前 20 个 PE 中枢基因。随后,我们创建了一个提名图,并进行了接收者操作特征(ROC)分析,以预测 PE 的风险。我们的分析,包括基因组富集分析(GSEA)和 PE DEGs 富集分析,揭示了基因在胎盘发育和免疫反应中的重要参与。我们确定了两个关键基因,即 BCL6 和 MME,并使用 5 组数据证实了它们的有效性。提名图显示了良好的诊断性能(AUC:0.82-0.96)。此外,我们还在病例组的系统性红斑狼疮外周血单核细胞(PBMCs)和 PE 胎盘标本中发现这两个基因的表达水平升高。对系统性红斑狼疮数据集中免疫浸润的分析表明,这两个基因的表达与中性粒细胞浸润之间存在很强的正相关性。在狼疮相关妊娠中,BCL6 和 MME 成为与 PE 的发生相关的关键基因,我们为此设计了一个提名图。这些发现为进一步研究诊断和了解 PE 的病理生理学提供了潜在的候选基因。
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Identification of Lupus-Associated Genes in the Pathogenesis of Pre-eclampsia Via Bioinformatic Analysis.

Pre-eclampsia (PE) is a severe pregnancy complication that is more common in patients with systemic lupus erythematosus (SLE). Although the exact causes of these conditions are not fully understood, the immune system plays a key role. To investigate the connection between SLE and PE, we analyzed genes associated with SLE that may contribute to the development of PE. We collected 9 microarray data sets from the NCBI GEO database and used Limma to identify the differentially expressed genes (DEGs). In addition, we employed weighted gene co-expression network analysis (WGCNA) to pinpoint the hub genes of SLE and examined immune infiltration using Cibersort. By constructing a protein-protein interaction (PPI) network and using CytoHubba, we identified the top 20 PE hub genes. Subsequently, we created a nomogram and conducted a receiver operating characteristic (ROC) analysis to predict the risk of PE. Our analysis, including gene set enrichment analysis (GSEA) and PE DEGs enrichment analysis, revealed significant involvement in placenta development and immune response. Two pivotal genes, BCL6 and MME, were identified, and their validity was confirmed using 5 data sets. The nomogram demonstrated good diagnostic performance (AUC: 0.82-0.96). Furthermore, we found elevated expression levels of both genes in SLE peripheral blood mononuclear cells (PBMCs) and PE placental specimens within the case group. Analysis of immune infiltration in the SLE data set showed a strong positive correlation between the expression of both genes and neutrophil infiltration. BCL6 and MME emerged as crucial genes in lupus-related pregnancies associated with the development of PE, for which we devised a nomogram. These findings provide potential candidate genes for further research in the diagnosis and understanding of the pathophysiology of PE.

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来源期刊
Bioinformatics and Biology Insights
Bioinformatics and Biology Insights BIOCHEMICAL RESEARCH METHODS-
CiteScore
6.80
自引率
1.70%
发文量
36
审稿时长
8 weeks
期刊介绍: Bioinformatics and Biology Insights is an open access, peer-reviewed journal that considers articles on bioinformatics methods and their applications which must pertain to biological insights. All papers should be easily amenable to biologists and as such help bridge the gap between theories and applications.
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