Dai Qianwen, Li Mengtao, Tian Xinping, Song Yijun, Zhao Jiuliang
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Bioinform Biol Insights. 2024 Aug 20;18:11779322241271558. doi: 10.1177/11779322241271558. eCollection 2024.
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.
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。尽管这些病症的确切病因尚未完全明确,但免疫系统起着关键作用。为了研究SLE与PE之间的联系,我们分析了与SLE相关且可能促成PE发生发展的基因。我们从NCBI基因表达综合数据库(GEO数据库)收集了9个微阵列数据集,并使用Limma软件来识别差异表达基因(DEGs)。此外,我们采用加权基因共表达网络分析(WGCNA)来确定SLE的核心基因,并使用Cibersort软件检测免疫浸润情况。通过构建蛋白质-蛋白质相互作用(PPI)网络并使用CytoHubba软件,我们确定了前20个PE核心基因。随后,我们创建了列线图并进行了受试者工作特征(ROC)分析以预测PE风险。我们的分析,包括基因集富集分析(GSEA)和PE差异表达基因富集分析,揭示了其在胎盘发育和免疫反应中的显著参与。我们鉴定出两个关键基因,即BCL6和MME,并使用5个数据集证实了它们的有效性。列线图显示出良好的诊断性能(曲线下面积:0.82 - 0.96)。此外,我们发现病例组中SLE外周血单个核细胞(PBMCs)和PE胎盘标本中这两个基因的表达水平均升高。对SLE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强正相关。BCL6和MME成为与PE发生发展相关的狼疮相关妊娠中的关键基因,为此我们设计了列线图。这些发现为进一步研究PE的诊断和理解其病理生理学提供了潜在的候选基因。