摘要
目的 筛选缺血性脑卒中后改变的内质网应激(Endoplasmic reticulum stress,ERS)相关基因,研究内质网应激与缺血性脑卒中之间的关系并确定生物标志物.方法 选取来自基因表达数据库(Gene ex-pression omnibus,GEO)的2个数据集(GSE28731和GSE30655),利用5个假手术(Sham)组和10个大脑中动脉栓塞(Middle cerebral artery occlusion,MCAO)组的遗传信息,分析差异表达基因(Differentially expressed genes,DEGs);筛选与内质网应激相关的差异表达基因(Endoplasmic reticulum stress-Differentially expressed genes,ERS-DEGs),进行富集分析以探索ERS-DEGs的生物功能和相关信号通路;进行蛋白质相互作用(Pro-tein-protein interaction,PPI)网络,以确定关键基因及其相关表达和功能.结果 本研究共鉴定出16个ERS-DEGs,通过基因本体论(Gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析证实,上调的ERS-DEGs主要富集在与氧化应激、肿瘤坏死因子(Tumor necrosis factor,TNF)、丝裂原活化蛋白激酶(Mitogen activated protein kinase,MAPK)和白细胞介素 17(Interleukin 17,IL-17)相关信号通路,最终通过PPI网络分析筛选出活化转录因子3(Activating transcription factor 3,ATF3)、Jun原癌基因(Jun proto-oncogene,Jun)等14个内质网相关的生物标志物.结论 通过整合和分析2个基因表达数据集,可以推断内质网应激可能参与缺血性脑卒中的发展,进而最终筛选出 14个内质网应激相关的差异基因,它们可能作为缺血性脑卒中诊断和治疗的潜在生物标志物.
Abstract
Objective To screen endoplasmic reticulum stress(ERS)-related genes after ischemic stroke(IS),to investigate the relationship between ERS and IS,and to identify biomarkers.Methods Two datasets(GSE28731 and GSE30655)were obtained from gene expression omnibus(GEO)and were subjected to inte-grated analysis.Differentially expressed genes(DEGs)were analyzed using genetic information from five sham samples and ten middle cerebral artery occlusion(MCAO)samples,and DEGs associated with ERS were iden-tified.Enrichment analysis was performed to explore the biological functions and related signaling pathways of ERS-related DEGs(ERS-DEGs).Protein-protein interaction(PPI)networks were constructed to identify key genes and their associated expression and functions.Results A total of 16 ERS-DEGs were identified in this study.Subsequently,the enrichment analysis using GO and KEGG confirmed that the upregulated ERS-DEGs were predominantly enriched in signaling pathways associated with oxidative stress,TNF,MAPK,and IL-17.Finally,14 endoplasmic reticulum-related biomarkers were selected through PPI network analysis.Conclusion By integrating and analyzing two gene expression datasets,it is possible to infer that ERS may be involved in the development of IS.This study ultimately identified 14 ERS-related DEGs that may serve as po-tential diagnostic and therapeutic biomarkers for IS.
维普
万方数据