基于加权基因共表达网络分析识别肥胖型多囊卵巢综合征的关键基因

Identification of key genes in obese polycystic ovary syndrome on WGCNA

目的 采用加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)方法识别肥胖型多囊卵巢综合征(polycystic ovary syndrome, PCOS)的关键基因,探讨肥胖型PCOS的发病机制。方法 从基因表达数据库(gene expression omnibus, GEO)下载GSE5090芯片数据,通过WGCNA算法分析筛选基因共表达关键模块和核心基因,对关键模块进行GO和KEGG分析,对核心基因进行差异分析以确定肥胖型PCOS的关键基因。结果 在GSE5090芯片数据中,通过WGCNA分析构建出了31个共表达基因模块,其中重褐色模块(MEsaddlebrown)与肥胖型PCOS具有密切的相关性,包含53个基因。对此模块基因进一步筛选,识别出了ZNF492、MED17、CRABP1、KCNV2、KRI1、ACSBG2、MACO1、SCLY、CPSF1、MAGEA8 10个肥胖型PCOS核心基因。对此模块基因进行GO和KEGG分析发现相关基因与脂肪酸代谢关系密切,主要作用于核蛋白,通过调节染色体组织、有机酸分解等发挥生物学功能。进一步对核心基因表达量进行差异分析,基因ZNF492、CRABP1、KCNV2在肥胖对照组与肥胖型PCOS脂肪组织间存在明显差异。结论 ZNF492、CRABP1和KCNV2基因在肥胖型PCOS的发展中可能产生重要生物学意义,其具体机制有待进一步研究。

Objective The key genes of obese polycystic ovary syndrome(PCOS)were identified by weighted gene co-ex-pression network analysis(WGCNA)to explore the pathogenesis of obese PCOS.Methods The GSE5090 chip data was download-ed from the Gene Expression Omnibus(GEO)database,and the key modules and core genes of gene co-expression were ana-lyzed and screened by WGCNA algorithm.GO and KEGG analysis was performed on the key modules,and difference analysis was performed on the core genes to determine the key genes of obese PCOS.Results WGCNA was used to analyze GSE5090 chip data,and 31 co-expressed gene modules were constructed,among which MEsaddlebrown module was closely correlated with obese PCOS,containing 53 genes.10 core genes of obese PCOS were identified,including ZNF492,MED17,CRABP1,KC-NV2,KRI1,ACSBG2,MACO1,SCLY,CPSF1 and MAGEA8.Go and KEGG analysis of this module gene showed that the re-lated genes were closely related to fatty acid metabolism,mainly acted on nuclear proteins,and played biological functions by regulating chromosome tissue and organic acid decomposition.Further analysis of the difference of core gene expression showed that there were significant differences in genes ZNF492,CRABP1 and KCNV2 between obese control group and obese PCOS adi-pose tissue.Conclusion ZNF492,CRABP1 and KCNV2 genes may have important biological significance in the development of obese PCOS,and their specific mechanisms need to be further studied.