基于GEO数据库筛选稳定性心绞痛患者外周血关键差异基因及诊断模型构建  

Identification of Hub Genes and Differential Expression Genes for Peripheral Blood Samples of Stable Angina Pectoris Based on GEO Databases

作　　者：侯芳霞 刘琳 张维[1] 方凤 齐婷 马美娟[1] 刘富强[1] 唐治国[1] HOU Fang-xia;LIU Lin;ZHANG Wei;FANG Feng;QI Ting;MA Mei-juan;LIU Fu-qiang;TANG Zhi-guo(Department of Cardiology,Shaanxi Provincial People’s Hospital,Xi’an 710068,China)

机构地区：[1]陕西省人民医院心血管内一科,西安710068

出　　处：《现代检验医学杂志》2022年第6期19-23,69,共6页Journal of Modern Laboratory Medicine

基　　金：陕西省重点研发项目(2021SF-329,2022SF-476);西安市科技计划项目(21YXYJ0095)。

摘　　要：目的通过生物信息学方法对稳定性心绞痛患者外周血基因表达谱芯片进行分析,获取其外周血表达谱特征并筛选关键差异表达基因作为潜在的分子标记物并构建Nomogram诊断模型。方法从NCBI中的基因表达综合(Gene Expression Omnibus,GEO)数据库中下载稳定性心绞痛患者和对照组的外周血基因表达谱芯片数据集GSE98583,使用R软件limma包筛选出具有显著意义的差异基因(differential expression genes,DEGs);利用clusterProfiler包进行基因本体(gene ontology,GO)与KEGG(kyoto encyclopedia of genes and genomes)通路富集分析;使用STRING在线分析工具构建蛋白交互网络和Cytoscape软件Cytohubba和Mcode插件筛选出关键基因;以关键基因为变量构建稳定性心绞痛Nomogram分子诊断预测模型。结果通过比较稳定性心绞痛患者和正常受试者外周血基因表达谱,共筛选出303个差异表达基因,其中上调基因160条,下调基因43条;GO和KEGG分析表明,这些差异表达基因主要参与神经递质配体受体相互作用、脂肪吸收消化、钙调节信号通路、PI3K-Akt通路、NF-kappaB通路及氧化磷酸化等有关,使用Cytohubba进一步分析,筛选出10个关键基因BDNF,GFAP,SYN1,NES,PLG,HPGDS,KCNC1,APOA4,AMBP和TJP1,并建立了Nomogram诊断模型。结论使用生物信息学方法揭示稳定性心绞痛外周血差异基因潜在特征,为稳定性心绞痛的早期诊断提供新的思路。Objective To analyze the peripheral blood gene expression profile of patients with stable angina pectoris using bioinformatics methods,obtain the characteristics of the peripheral blood gene expression profile,and screen hub genes as potential molecular markers and construct nomogram model.Methods The GSE98583 dataset was downloaded from the GEO database in NCBI,which contain the peripheral blood gene expression profile of stable angina patients and the control group.Differential expression genes(DEGs)were screen using the R software limma package.Further Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the clusterprofiler package.The STRING database and Cytohubba plug-in of Cytoscape software were used to establish and visualize the protein-protein interaction(PPI)network and identify the hub genes.Results A total of 303 differentially expressed genes were screened between stable angina pectoris and normal subjects,including 160 up-regulated genes and 43 down-regulated genes.GO and KEGG pathway enrichment analyses found that these genes mainly take part in the process of neuroactive ligand-receptor interaction,fat digestion and absorption,calcium signaling pathway,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,oxidative phosphorylation and so on.Ten key genes were identified by Cytohubba plug-in,including BDNF,GFAP,SYN1,NES,PLG,HPGDS,KCNC1,APOA4,AMBP,TJP1 and nomogram model was constructed based on these hub genes.Conclusion The bioinformatics method was used to reveal the potential characteristics of differential genes in peripheral blood of stable angina pectoris,providing a new idea for the early dragnosis of stable angina pectoris.

关 键 词：稳定性心绞痛 生物信息学 基因表达综合数据库 差异表达基因 富集分析 

分 类 号：R541.4[医药卫生—心血管疾病] Q343.1[医药卫生—内科学]