基于生物信息学分析慢性阻塞性肺疾病的关键基因及其与免疫浸润的关系

Analysis of Key Genes in Chronic Obstructive Pulmonary Disease and Their Relationship with Immune Infiltration Based on Bioinformatics.

目的通过生物信息学分析慢性阻塞性肺疾病(COPD)的关键基因,以及关键基因表达与COPD肺组织免疫浸润的关系。方法从GEO数据库下载基因芯片数据集GSE47460。使用R语言筛选正常组及COPD组样本并利用limma包鉴定差异表达基因(DEGs),使用ClusterProfiler包对DEGs进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析。利用String数据库及Cytoscape软件对DEGs构建蛋白互作网络(PPI)并筛选关键基因。分析关键基因在正常组与COPD组以及在COPD组内不同严重程度的差异表达。绘制受试者工作特征曲线(ROC)评估关键基因对COPD不同严重程度的诊断性能。应用单样本基因富集分析(ssGSEA)评估关键基因表达与COPD肺组织免疫浸润的关系。结果筛选出DEGs 75个,上调基因47个[矫正后P<0.05及log 2(差异倍数)≥0.5],下调基因28个[矫正后P<0.05及log 2(差异倍数)≤-0.5]。鉴定了3个在COPD组高表达且与COPD严重程度呈正相关的关键基因,分别是CD19、TNFRSF13B、POU2AF1。免疫浸润分析结果表明,COPD肺组织TNFRSF13B高表达组的免疫浸润程度更高。结论通过生物信息学分析方法,筛选得到TNFRSF13B为COPD发病机制中的关键基因,且与COPD严重程度及肺组织免疫浸润密切相关,为COPD发病机制的研究提供一定的参考。

Objective To identify key genes in chronic obstructive pulmonary disease(COPD)and relationship between ke genes and immune infiltration in COPD lung tissue by bioinformatics analysis.Methods Gene chip dataset GSE47460 from GEO database was downloaded.Samples of normal and COPD group were screened by R software,and differential expressed genes(DEGs)were identified by limma package.GO and KEGG enrichment analysis of DEGs were analyzed by ClusterProfiler package.String database and Cytoscape software were used to construct PPI network for DEGs and screen key genes.Differential expression of key genes between normal and COPD groups and within COPD groups with different severities were analyzed.Plotting ROC curves were used to evaluate diagnostic performance of key genes for different severity of COPD.Application of ssGSEA was used to evaluate relationship between key gene expression and immune infiltration in COPD lung tissue.Results The number of DEGs was 75,of which 47 were up-regulated[adj.P<0.05 and log 2(FC)≥5]and 28 were down regulated[adj.P<0.05 and log 2(FC)≤-0.5].Three key genes were identified,which were highly expressed in COPD group and positively correlated with the severity of COPD,namely CD19,TNFRSF13B and POU2AF1.Results of immune infiltration analysis showed that degree of immune infiltration was higher in the group with high expression of TNFRSF13B in COPD lung tissue.Conclusion Based on bioinformatics analysis,TNFRSF13B was screened as a key gene in the pathogenesis of COPD,and was closely related to the severity of COPD and immune infiltration of lung tissue,so as to provide a certain reference for the study of the pathogenesis of COPD.