胎盘病因不明绒毛炎发病关键基因筛选  

Screening of Key Genes for Villitis of Unknown Etiology

作　　者：陈义凤 谭丽萍 杨春雪 陈雪梅[1,2] 何俊琳 高茹菲[1,2] CHEN Yifeng;TAN Liping;YANG Chunxue;CHEN Xuemei;HE Junlin;GAO Rufei(Department of Reproductive Biology,School of Public Health,Chongqing Medical University,Chongqing 400016,China;Reproductive and Developmental Joint Laboratory of International Cooperation,the Ministry of Education,Chongqing 400016,China)

机构地区：[1]重庆医科大学公共卫生学院,重庆400016 [2]生殖与发育教育部国际合作联合实验室,重庆400016

出　　处：《西南大学学报（自然科学版）》2024年第8期45-53,共9页Journal of Southwest University(Natural Science Edition)

基　　金：重庆市自然科学基金项目(cstc2020jcyj-msxmX0041).

摘　　要：目的分析胎盘病因不明绒毛炎(Villitis of Unknown Etiology,VUE)可能的发病机制,筛选出在疾病中起关键作用的靶基因.方法从基因表达综合数据库(Gene Expression Omnibus,GEO)中下载VUE及正常对照组织的基因表达谱数据.通过加权基因共表达网络分析(Weighted Correlation Network Analysis,WGCNA)和基因差异表达分析识别关键的VUE基因.使用基因本体论(Gene Ontology,GO)以及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析VUE可能的发病机制.通过蛋白质蛋白质相互作用(Protein-protein Interaction,PPI)对关键VUE基因进一步筛选发现VUE核心靶基因;最后通过受试者工作特征(Receiver Operating Characteristic,ROC)曲线和单因素逻辑回归对核心靶基因进行分析.结果通过加权基因共表达网络(WGCNA)分析和基因差异表达分析,发现了206个VUE核心基因,对其进行功能分析发现这些核心VUE基因主要在跨膜受体蛋白丝氨酸/苏氨酸的负调控、细胞结构组织和细胞外基质结构成分等功能上富集,而富集通路主要包括Hippo信号通路、TGF信号通路和Wnt信号通路等.利用这206个关键基因构建PPI网络筛选出10个VUE核心靶基因,对其进行分析发现它们均可作为识别VUE的独立因素,且其中9个基因与VUE发生风险呈显著负相关关系.结论发现了几种VUE发生发展的可能作用机制,且MRPL13,FBN1,CTGF,SLC2A10,SLIRP,CAV1,WNT5A,VAMP7,PPP1CB,VBP1有望成为VUE诊断和治疗的生物标志物.Objective of this study is to analyze the possible development mechanisms of villitis of unknown etiology(VUE)and the screening of target genes that play a key role in the disease.Gene expression profile data of VUE patients and healthy individuals were downloaded from the Gene Expression Omnibus(GEO).Bioinformatics methods were applied to perform a weighted correlation network analysis(WGCNA)and gene differential expression analysis to identify key VUE genes.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were used to discover the possible mechanisms of action.Key VUE genes were further screened by protein-protein interactions(PPI)to identify core VUE target genes.Finally,the core target genes were analyzed by ROC curve and univariate logistic regression.By WGCNA analysis and gene differential expression analysis,206 VUE core genes were identified.Functional analysis found that these core VUE genes were mainly enriched in the negative regulation of the transmembrane receptor protein serine/threonine,cellular structural organization and extracellular matrix structural components,while the enriched pathways mainly included Hippo signaling pathway,TGF signaling pathway and Wnt signaling pathway.10 VUE core target genes were selected from 206 key genes.Finally,the analysis of the 10 core target genes found that they all could be used as independent factors to identify VUE,and 9 genes showed a significant negative correlation with the risk of developing VUE.This study found several possible mechanisms of the occurrence and development of VUE,and MRPL13,FBN1,CTGF,SLC2A10,SLIRP,CAV1,WNT5A,VAMP7,PPP1CB and VBP1 are expected to become biomarkers for the diagnosis and treatment of VUE.

关 键 词：胎盘病因不明绒毛炎 加权基因共表达网络分析 靶基因 

分 类 号：Q987[生物学—遗传学] R711[生物学—人类学]