创伤后脓毒症关键基因筛选及其与免疫基因相关性的生物信息学分析  

Screening of key genes in post-traumatic sepsis and bioinformatics analysis of their correlation with immune genes

作　　者：庄良明 王冠珠 王鹏飞 王晓静 张文媛 顾忠民[1] 陈嵘[4] Zhuang Liangming;Wang Guanzhu;Wang Pengfei;Wang Xiaojing;Zhang Wenyuan;Gu Zhongmin;Chen Rong(Department of Critical Care Medicine,Fuzhou Second Hospital,Fuzhou 350007,Fujian,China;Department of Critical Care Medicine,Qitai County People’s Hospital,Changji 831800,Xinjiang Uygur Autonomous Region,China;Department of Scientific Research and Teaching,Fuzhou Second Hospital,Fuzhou 350007,Fujian,China;Department of Musculoskeletal Cancer Surgery,Fuzhou Second Hospital,Fuzhou 350007,Fujian,China)

机构地区：[1]福州市第二医院重症医学科,福建福州350007 [2]奇台县人民医院重症医学科,新疆昌吉831800 [3]福州市第二医院科研教学部,福建福州350007 [4]福州市第二医院骨与软组织肿瘤科,福建福州350007

出　　处：《创伤与急诊电子杂志》2024年第1期14-26,共13页Journal of Trauma and Emergency(Electronic Version)

基　　金：福建省创伤骨科急救与康复临床医学研究中心项目(2020Y2014)。

摘　　要：目的基于生物信息学方法分析创伤后脓毒症的关键基因及其与免疫基因相关性。方法从基因表达数据库(geneexpressionomnibus,GEO)中下载GSE12624数据集,筛选创伤后脓毒症患者外周血中差异基因,对差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyotoencyclopediaofgenesandgenomes,KEGG)富集分析,使用String、Cytoscape构建蛋白质-蛋白质互作网络(Protein-Protein Interaction Networks,PPI)及基于Cytohubba插件选出关键基因,通过受试者操作特征曲线的曲线下面积选出枢纽基因,验证其在创伤后脓毒症中的表达情况,通过基因集富集分析(gene set enrichment analysis,GSEA)、基因集变异分析(gene set variation analysis,GSVA)、免疫浸润分析以及分析其与免疫基因、免疫细胞相关性。结果在GSE12624数据集中获得362个差异基因,GO富集分析示差异基因参与信号转导、细胞凋亡、炎症反应相关的生物学过程,KEGG富集分析示,差异基因主要富集在补体和凝血级联通路、细胞周期等信号通路;选出曲线下面积最大值(0.815)的基因AURKB作为创伤后脓毒症的枢纽基因,其在创伤后脓毒症中高表达;通过GSEA富集分析显示AURKB高表达组主要富集到代谢、细胞周期、P53信号通路等相关的基因集,GSVA富集分析显示AURKB高表达组主要集到糖胺聚糖降解、花生四烯酸代谢通路、焦点黏附通路等相关途径;AURKB的表达与免疫基因(IL21R、CXCL10)的表达、免疫细胞(初始CD4+T细胞、滤泡辅助性T细胞)浸润呈正相关。结论AURKB在创伤后脓毒症中表达上调,参与创伤后脓毒症的免疫调节通路,可作为创伤后脓毒症早期预警的分子标志物及干预潜在靶标。Objective To analyze the key genes of post-traumatic sepsis and their correlation with immune genes based on bioinformatics methods.Method The GSE12624 dataset was downloaded from the Gene Expression Omnibus(GEO)database,and differentially expressed genes(DEGs)in patients with posttraumatic sepsis were identified.Analyses of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment were conducted on differential genes.The protein-protein interaction network(PPI)was constructed using String and Cytoscape,and the key genes were selected based on the Cytohubba plugin.The hub genes were selected based on the area under the curve of the receiver operating characteristic curve to verify their expression in post-traumatic sepsis.Gene Set Enrichment Analysis(GSEA),Gene Set Variation Analysis(GSVA),and immune infiltration analysis were used to analyze the correlation between them and immune genes and immune cells.Result A total of 362 differentially expressed genes were obtained in the GSE12624 dataset.GO enrichment analysis showed that the differentially expressed genes were involved in biological processes related to signal transduction,apoptosis,and the inflammatory response.The differentially expressed genes were mainly associated with the complement and coagulation cascade pathway,the cell cycle,and other signaling pathways,according to the KEGG enrichment analysis.The gene AURKB,with the maximum area under the curve(0.815),was selected as the pivotal gene of post-traumatic sepsis,and it is highly expressed in post-traumatic sepsis.GSEA enrichment analysis showed that the AURKB high expression group was mainly enriched in gene sets related to metabolism,cell cycle,P53 signaling pathway,and GSVA enrichment analysis showed that the AURKB high expression group was mainly enriched in glycosaminosan degradation,arachidonic acid metabolism,focal adhesion pathway and other related pathways.AURKB was positively correlated with immune genes(IL21R,CXCL10)and immune cells(naive CD4+T cells,follicular helper T

关 键 词：脓毒症 基因 创伤 免疫 生物信息 

分 类 号：R641[医药卫生—外科学] Q811.4[医药卫生—临床医学]