摘要
目的:基于生物信息学技术对宫内生长受限(IUGR)的芯片数据进行基因集富集分析(GSEA)以及关键差异基因的免疫浸润分析,并预测相关的作用中药。方法:从基因表达数据库(GEO)中获取GSE12216芯片数据,运用R软件筛选出差异表达基因(DEGs)。利用R包对数据集所有基因进行GSEA的基因本体论(GO)与京都基因与基因组百科全书(KEGG)分析以及DEGs的GO和KEGG分析;通过STRING数据库构建DEGs蛋白交互作用网络以及Cytohubba筛选关键基因;对关键基因进行ROC分析判断关键基因的诊断价值;通过单样本基因集富集分析(ssGSEA)算法获得24种免疫细胞在IUGR的含量及比例进行分析;通过Spearman统计方法计算关键基因表达与免疫细胞浸润的相关性,并利用Coremine数据库对免疫相关的关键基因进行中药预测。结果:共获得228个IUGR与正常胎盘的DEGs;GSEA结果显示IUGR样本的基因表达改变主要涉及趋化因子与受体以及溶酶体信号通路等过程;DEGs的GO和KEGG分析显示DEGs主要富集在肿瘤坏死因子(TNF)信号通路、缺氧诱导因子1(HIF-1)信号通路和Janus激酶/信号转导与转录激活子(JAK/STAT)信号通路;Cytohubba共筛选出10个关键基因:CSF2、IRAK1、PTGS2、FLT1、CHUK、CXCL12、FOS、LEP、CXCL2以及RELB;ROC分析显示这10个基因均有较高的诊断价值;免疫细胞的浸润矩阵分析结果表明,在IUGR胎盘组织中自然杀伤T细胞(NKT)以及单核细胞变化显著。免疫浸润与关键基因的相关性分析发现CSF2、IRAK1、PTGS2、CHUK、CXCL12、CXCL2以及RELB 7个基因与免疫浸润有相关性,中药预测发现,人参、黄芪与IUGR相关免疫浸润的关系最为密切。结论:NKT细胞与单核细胞在IUGR的发生发展中具有重要作用;共鉴定出7个与免疫浸润相关的关键基因;人参及黄芩可作为IUGR治疗的药物来源。
Objective:Based on bioinformatics technology,gene set enrichment analysis(GSEA)and immune infiltration analysis of key differential genes were performed on the chip data of intrauterine growth restriction(IUGR),and the related effects of traditional Chinese medicine were predicted.Methods:GSE12216 chip data were obtained from Gene Expression Omnibus(GEO),and differentially expressed genes(DEGs)were screened by the R software.Then,Gene Set Enrichment Analysis(GSEA)was used to analyze gene ontology(GO)functional and Kyoto encyclopedia of genes and genome(KEGG)for all expression data,and GO and KEGG of DEGs were analyzed by the R-package.The DEGs protein interaction network was constructed by STRING database,and the key genes were screened by Cytohubba;ROC analysis of key genes to judge the diagnostic value of key genes;contents and proportion of 24 immune cells in IUGR were obtained by single sample gene set enrichment analysis(ssGSEA);the correlation between key gene expression and immune cell infiltration was calculated by Spearman statistical analysis,and the immune related key genes were pre-dicted by Coremine database.Results:Total 228 IUGR and DEGs of normal placenta were obtained;GSEA results showed that the gene expression changes of IUGR samples were mainly related to chemokines,receptors and lysosomal signal pathway;GO and KEGG analysis of DEGs showed that DEGs were mainly enriched in TNF signaling pathway,HIF-1 signaling pathway and JAK/STAT signal-ing pathway;Cytohubba screened 10 key genes:CSF2,IRAK1,PTGS2,FLT1,CHUK,CXCL12,FOS,LEP,CXCL2 and RELB;ROC analysis showed that these 10 genes had high diagnostic value;infiltration matrix analysis of immune cells revealed that natural killer T cells(NKTs)and monocytes appeared significantly altered in IUGR placentas.The correlation analysis between immune infil-tration and key genes found that seven genes CSF2,IRAK1,PTGS2,CHUK,CXCL12,CXCL2 and RELB were correlated with im-mune infiltration.According to the prediction of traditional Chinese medicine,it was found
作者
杜志欣
刘岳轩
张一格
江煜
张桐
杨丽萍
DU Zhixin;LIU Yuexuan;ZHANG Yige;JIANG Yu;ZHANG Tong;YANG Liping(School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China;The Second Clinical College of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2024年第2期225-232,共8页
Chinese Journal of Immunology
基金
国家自然科学基金面上项目(81973596)
河南省科技攻关项目(212102310341)。
关键词
生物信息学
宫内生长受限
GSEA
免疫浸润
中药预测
Bioinformatics
Intrauterine growth restriction
GSEA
Immune infiltration
Prediction of traditional Chinese medicine
