酒精使用障碍的潜在关键基因生物信息学分析

Identification of potential hub genes involved in alcohol use disorder via bioinformatics analysis

背景酒精使用障碍(AUD)是一类慢性复发性脑病,遗传因素在AUD的发病过程中起重要作用。明确AUD的关键分子标志物对于进一步阐明疾病的发病机制,探索新的治疗靶点和预防复发具有重要意义。目的应用生物信息学方法,筛选AUD的核心基因和信号通路,为AUD的防治提供新的方向。方法从基因表达综合数据库(GEO)下载基因表达数据集GSE161986。应用R软件的limma包筛选差异表达基因(DEGs)。使用DAVID数据库进行基因富集分析(GSEA)。使用STRING数据库和Cytoscape软件构建蛋白-蛋白互作网络(PPI)并寻找网络核心基因。使用GSE44456验证筛选潜在核心基因。结果共筛选出114个DEGs。富集分析表明,差异基因主要参与信号转导、蛋白结合、细胞膜以及MAPK信号通路等功能的调控。PPI及验证分析显示,GAD1、TIMP1和CD44可能是AUD发病的潜在关键基因。结论GAD1和TIMP1表达异常以及MAPK信号通路可能在AUD的发病过程中起关键作用,并可能作为AUD诊断和治疗的潜在分子靶点。

Background Alcohol use disorder(AUD)is a type of chronic relapsing brain disorder.Genetic factors play an important role in the pathogenesis of AUD.And screening for molecular markers of AUD is of great significance for further elucidating the pathogenesis of the disease,discovering novel therapeutic targets and preventing relapse.Objective To explore relevant hub genes and potential signal pathways associated with the development of AUD through bioinformatics analysis,and to provide a new direction for the prevention and treatment of AUD.Methods The GSE161986 dataset was acquired from the Gene Expression Omnibus(GEO)database.The limma package in R was utilized to identify differentially expressed genes(DEGs).Gene set enrichment analysis(GSEA)was carried out using the Database for Annotation,Visualization and Integrated Discovery(DAVID).A protein–protein interaction(PPI)network of DEGs was assessed using the STRING database and visualized by Cytoscape software.Finally,hub genes were validated in GSE44456 dataset.Results A total of 114 DEGs were identified.GSEA revealed that these genes were mainly involved in the regulation of signal transduction,protein binding,membrane trafficking and MAPK signaling pathway.PPI network and validation study indicated that GAD1,TIMP1 and CD44 were potential hub genes involved in AUD.Conclusion Aberrant expression of GAD1 and TIMP1 as well as MAPK signaling pathway may play a key role in the pathogenesis of AUD,and may serve as potential molecular targets for the diagnosis and treatment of AUD.