使用GEO数据库筛选哮喘患者气道平滑肌细胞中差异表达的关键基因  

Screening of key genes differentially expressed in airway smooth muscle cells of asthmatic patients using GEO database

作　　者：向霖丽 高亚东[1] XIANG Linli;GAO Yadong(Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学中南医院,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2021年第5期818-824,共7页Medical Journal of Wuhan University

摘　　要：目的:基于GEO数据库初步分析健康人和哮喘患者气道平滑肌细胞的差异表达基因,为治疗哮喘提供更多的可能。方法:检索GEO数据库中关于哮喘患者气道平滑肌细胞的相关基因芯片数据(Microarray),借助R语言分析差异基因,利用DAVID数据库对关键差异基因进行GO富集分析和KEGG通路分析,构建差异基因蛋白质-蛋白质相互作用关系(PPI)网络,拓扑筛选关键的差异表达基因。结果:检索GEO数据库确定序列号为隶属于GPL6224平台的GSE35643和GSE63383芯片和隶属于GPL6480的GSE34313芯片,利用R语言分析筛选出不同处理组的差异基因,通过DAVID在线功能富集分析关键差异基因,显示GO富集主要表现为巨噬细胞细胞因子生成的正向调控、细胞黏附、缺氧的反应、成纤维细胞生长因子受体信号通路的负向调控、炎症反应的正向调控、白细胞介素-6生成的正向调控、膀胱发育、肺发育、ERK1和ERK2级联、细胞骨架构建、肌动蛋白丝聚合的正向调控等;在KEGG通路富集层面主要集中在肾素分泌、ABC转运体、补体和凝血级联、轴突引导蛋白质的消化和吸收、PPAR信号通路、黏蛋白型O-聚糖生物合成、细胞因子与受体的相互作用、肥厚型心肌病、脂肪酸代谢、细胞周期、以及Hippo信号通路等;通过String数据库构建PPI,以MCC权重≥3为标准,在各处理组共拓扑筛选出52个关键差异基因;将不同数据集中获得的差异基因进行比对,最终得出4个在所有样本中均有表达差异的关键基因:前列腺素内过氧化物合成酶2(PTGS2)、骨形态发生蛋白4(BMP4)、透明质酸合酶2(HAS2)、肿瘤坏死因子配体超家族成员4(TNFSF4)。结论:PTGS2、BMP4、HAS2和TNFSF4可能在哮喘的发病过程中发挥着重要作用。Objective: To analyze the differentially expressed genes(DEGs) of airway smooth muscle cells(ASMCs) between healthy and asthmatic patients based on GEO database. Methods: Microarray data of airway smooth muscle cells from asthmatic patients and healthy people were retrieved from GEO database. DEGs were analyzed by R language, and GO enrichment and KEGG pathway analysis on these DEGs were performed by DAVID database. Construction of protein-protein interaction(PPI)network and topological screening of key DEGs were performed. Results: We got three datasets from GEO database: GSE35643 and GSE63383 in GPL6224 platform and GSE34313 in GPL6480 platform. R software were used to screen for DEGs in each group. Functional enrichment analysis of key differential genes showed that GO enrichment were mainly focused on the positive regulation of macrophage cytokine production, cell adhesion, hypoxia response, negative regulation of fibroblast growth factor receptor signaling pathway, positive regulation of inflammatory response, positive regulation of interleukin-6 production, bladder development, lung development, ERK1 and ERK2 cascade, cytoskeleton construction, actin filament polymerization and so on;KEGG pathway enrichment were mainly focused on renin secretion, ABC transporter, complement and coagulation cascade, axon guided protein digestion and absorption, PPAR signaling pathway, mucopolysaccharide biosynthesis, cytokine receptor interaction, hypertrophic cardiomyopathy, fatty acid metabolism, cell cycle, and Hippo signaling pathway, etc.. Using String database to construct PPI network and Cytoscape software to screen key DEGs, taking MCC weight≥3 as the screen standard, totally 52 key DEGs were selected in each group. Then the key DEGs were mapped with data in GSE34313, and four hub genes were obtained: prostaglandin endoperoxide synthase 2(PTGS2), bone morphogenetic protein 4(BMP4),hyaluronic acid synthase 2(HAS2), and TNFSF4. Conclusion: PTGS2, BMP4, HAS2, and TNFSF4 may paly important roles in asthma.

关 键 词：哮喘 气道平滑肌细胞 气道重塑 生物信息学 GEO数据库 R语言 差异基因 

分 类 号：R562.25[医药卫生—呼吸系统]