基于生物信息学分析筛选儿科脓毒症关键基因  

Screening and analysis of hub genes for pediatric sepsis based on bioinformatics

作　　者：浦浩萍 张秀彩 Pu Haoping;Zhang Xiucai(Department of Clinical Laboratory,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310003,China)

机构地区：[1]浙江大学医学院附属儿童医院实验检验中心、国家儿童健康与疾病临床医学研究中心,杭州310003

出　　处：《中华检验医学杂志》2023年第2期183-188,共6页Chinese Journal of Laboratory Medicine

摘　　要：目的应用生物信息学方法筛选和分析儿科脓毒症关键基因。方法从GEO数据库中下载2015年2月19日上传的儿科脓毒症芯片数据集GSE66099和2020年2月13日上传的儿科脓毒症芯片数据集GSE145227,使用Limma包筛选儿科脓毒症与正常对照组血液组织差异表达信使核糖核酸(DEmRNA),随后进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用在线网站STRING和Cytoscape软件对DEmRNA构建蛋白互作网络(PPI),并筛选关键(hub)基因。最后使用R软件进行hub基因差异表达和受试者工作特征曲线(ROC曲线)分析。结果共发现160个DEmRNA,包含126个上调mRNA和34个下调mRNA。通过GO功能富集分析,发现DEmRNA主要富集在中性粒细胞激活和脱粒,T细胞激活以及淋巴细胞活化调节。KEGG富集通路分析显示DEmRNA主要参与自然杀伤细胞介导的细胞毒性和中性粒细胞胞外陷阱的形成。STRING和Cytoscape共筛选出10个hub基因,通过R软件分析发现10个hub基因(ARG1、RETN、MMP9、C3AR1、LCN2、FPR2、CCL5、CEACAM8、ELANE和DEFA4)在儿科脓毒症中具有显著的差异表达,同时每个hub基因的ROC曲线下面积均>0.7,具有较好的诊断价值。结论通过生物信息学分析获得10个hub基因在儿科脓毒症疾病进展中发挥重要作用,并为儿科脓毒症诊断、预后标志物和潜在治疗靶点提供了新的理论依据。Objective To screen and analyze the hub genes/gene panel for pediatric sepsis by bioinformatics methods.Methods The pediatric sepsis chip datasets GSE66099 uploaded on Feb 19,2015 and GSE145227 uploaded on Feb 13,2020 were obtained from the gene expression omnibus(GEO)database and used to screen out the differentially expressed mRNA(DEmRNA)by the limma package.The Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied and performed for the functional and pathway enrichment analysis subsequently.The online database STRING and Cytoscape software were used to construct a protein interaction network(PPI)for DEmRNA and screen the hub gene.R package was used to analyze the expression and diagnostic significance of hub genes.Results In this study,160 total DEmRNA including 126 up-regulated mRNA and 34 down-regulated mRNA were obtained.By GO functional enrichment analysis,the results showed that DEmRNA were mainly enriched and focused on these areas:neutrophil activation,neutrophil degranulation,T cell activation and regulation of lymphocyte activation.KEGG enrichment pathway analysis showed that DEmRNA was mainly involved in signaling pathways including natural killer cell-mediated cytotoxicity and neutrophil extracellular trap formation.Ten DEGs(ARG1,RETN,MMP9,C3AR1,LCN2,FPR2,CCL5,CEACAM8,ELANE and DEFA4)as hub genes were screened by STRING and Cytoscape.A gene panel with 10 members had significant differences and the area under the ROC curve of each hub gene was greater than 0.7.Conclusion By bioinformatics analysis,we find 10 genes that play an important role in the progression of pediatric sepsis,and provide a new theoretical basis for the diagnosis,prognostic markers and potential therapeutic targets of pediatric sepsis.

关 键 词：儿科学 脓毒症 信息学 诊断 标志物 

分 类 号：R720.597[医药卫生—急诊医学] Q811.4[医药卫生—儿科]