Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
J Asthma. 2023 Feb;60(2):348-359. doi: 10.1080/02770903.2022.2051544. Epub 2022 Mar 21.
Asthma is a chronic airway inflammatory disease caused by multiple genetic and environmental factors. This study mainly sought to provide potential therapeutic targets and biomarkers for neutrophilic asthma (NA).
Three gene expression profiling datasets were obtained from the Genome Expression Omnibus (GEO) database. GSE45111 and GSE41863 were used to identify hub genes and potential biomarkers, and GSE137268 was used for data verification. We verified the repeatability of intragroup data and identified differentially expressed genes (DEGs). Then, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs, and a protein-protein interaction (PPI) network was constructed to identify the hub genes. Finally, receiver operating characteristic (ROC) analysis was used to verify the ability of the hub genes to differentiate between NA and eosinophilic asthma (EA).
In this study, we identified 411 DEGs by comprehensive analysis of NA/EA patients and NA/healthy controls (HCs). Ten hub genes (CXCR1, FCGR3B, CXCR2, SELL, S100A12, CSF3R, IL6R, JAK3, CD48, and GNG2) were identified from the PPI network. Finally, based on the ROC analysis, 7 genes showed good diagnostic value for discriminating NA from EA-CXCR1, FCGR3B, CXCR2, SELL, S100A12, CSF3R, and IL6R (AUC > 0.7).
We identified 7 hub genes that can distinguish NA from EA. The IL-8-mediated signaling may be the primary pathway to determine the NA phenotype in asthma. CXCR1/2 and S100A12 may be the primary genes determining the NA phenotype. CXCR1/2 and S100A12 might be biomarkers and new therapeutic targets for NA.
Supplemental data for this article is available online at at.
哮喘是一种由多种遗传和环境因素引起的慢性气道炎症性疾病。本研究主要旨在为中性粒细胞性哮喘（NA）提供潜在的治疗靶点和生物标志物。
从基因组表达综合数据库（GEO）中获得了三个基因表达谱数据集。GSE45111 和 GSE41863 用于识别枢纽基因和潜在的生物标志物，GSE137268 用于数据验证。我们验证了组内数据的可重复性，并确定了差异表达基因（DEGs）。然后，我们对 DEGs 进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，并构建了蛋白质-蛋白质相互作用（PPI）网络以识别枢纽基因。最后，使用接收器工作特征（ROC）分析验证了枢纽基因区分 NA 和嗜酸性粒细胞性哮喘（EA）的能力。
在这项研究中，我们通过综合分析 NA/EA 患者和 NA/健康对照（HC），鉴定出 411 个 DEGs。从 PPI 网络中鉴定出 10 个枢纽基因（CXCR1、FCGR3B、CXCR2、SELL、S100A12、CSF3R、IL6R、JAK3、CD48 和 GNG2）。最后，基于 ROC 分析，7 个基因（CXCR1、FCGR3B、CXCR2、SELL、S100A12、CSF3R 和 IL6R）在区分 NA 与 EA 方面具有良好的诊断价值（AUC>0.7）。
我们鉴定出 7 个可区分 NA 与 EA 的枢纽基因。IL-8 介导的信号通路可能是决定哮喘中 NA 表型的主要途径。CXCR1/2 和 S100A12 可能是决定 NA 表型的主要基因。CXCR1/2 和 S100A12 可能是 NA 的生物标志物和新的治疗靶点。
