基于加权基因共表达网络分析鉴定PE患者的潜在生物标志物  

Identification of Potential Biomarkers in Patients with Preeclampsia Based on Weighted Gene Co-Expression Network

作　　者：张慧杰 曲洪美[1] 马江磊 Zhang Huijie;Qu Hongmei;Ma Jianglei(Department of Obstetrics,Yantai Yuhuangding Hospital,Yantai 264000,China;Department of Infectious Diseases,Yantai Qishan Hospital,Yantai 264000,China)

机构地区：[1]烟台毓璜顶医院产科,山东烟台264000 [2]烟台市奇山医院感染性疾病科,山东烟台264000

出　　处：《巴楚医学》2024年第1期44-49,共6页Bachu Medical Journal

基　　金：山东省自然科学基金项目(No:ZR2021MH223)。

摘　　要：目的:本研究旨在通过对子痫前期(PE)患者基因数据集进行加权基因共表达网络分析(WGCNA),寻找PE的分子标志物。方法:从GEO数据库下载GSE10588表达数据集,该数据集包括17例PE患者和26例对照者的胎盘组织转录组数据。使用差异表达分析及WGCNA筛选与PE相关的重点差异表达基因(DEGs),利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析来探索重点基因的生物学作用。构建蛋白-蛋白相互作用(PPI)网络筛选关键枢纽基因,并通过风险预测模型和受试者工作特征(ROC)曲线评价这些枢纽基因对PE的预测效果。结果:共获得138个DEGs,其中包括100个上调和38个下调DEGs。通过WGCNA确定了23个与PE发病最相关的重点DEGs。GO和KEGG通路分析显示,这些重点DEGs在调节促性腺激素分泌、白细胞分化、造血功能、内分泌功能及B细胞的激活等生物学作用中发挥重要作用。在PPI网络中,卵泡抑素相关基因3(FSTL3)、酪氨酸激酶受体1(FLT1)、抑制素亚单位A(INHBA)、N-myc下游调节基因1(NDRG1)和瘦素(LEP)等成为节点最多的基因。风险预测和ROC曲线表明,FSTL3和LEP具有较高的风险得分和诊断价值。结论:FSTL3和LEP可以作为预测和诊断PE的生物标志物。Objective:To search for molecular markers of preeclampsia(PE)by using weighted gene coexpression network analysis(WGCNA)on a genetic dataset of patients with preeclampsia(PE).Methods:The GSE10588 expression dataset was downloaded from the GEO database and included placental tissue transcriptome data from 17 PE patients and 26 controls.Differential expression analysis and WGCNA were used to screen key differentially expressed genes(DEGs)associated with PE,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were used to explore the biological roles of key genes.The protein-protein interaction(PPI)network was constructed to screen key hub genes,and the predictive effect of these hub genes on PE was evaluated by risk prediction model and receiver operating characteristic(ROC)curve.Results:A total of 138 DEGs were obtained,including 100 up-regulated and 38 down-regulated DEGs.The WGCNA identified 23 key DEGs that were most associated with the onset of PE.GO and KEGG pathway analysis showed that these key DEGs play an important role in regulating gonadotropin secretion,leukocyte differentiation,hematopoietic function,endocrine regulation,and B-cell activation.In the PPI network,follistatin-related gene 3(FSTL3),tyrosine kinase receptor 1(FLT1),statin subunit A(INHBA),N-myc downstream regulatory gene 1(NDRG1)and leptin(LEP)were the genes with the most nodes.Risk prediction and ROC curve showed that FSTL3 and LEP had high risk scores and diagnostic value.Conclusion:FSTL3 and LEP can be used as biomarkers for the prediction and diagnosis of PE.

关 键 词：子痫前期 加权基因共表达网络分析 生物标志物 卵泡抑素相关基因3 瘦素 

分 类 号：R714.25[医药卫生—妇产科学]