Identification of potential biomarkers and pathogenesis in neutrophil-predominant severe asthma: A comprehensive bioinformatics analysis.

Shuanglan Xu, Zi Chen, Linyang Ge, Chenhui Ma, Quan He, Weihua Liu, Liuchao Zhang, Linfu Zhou

Medicine 2022 Sep 23

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Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis. Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified. Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma. This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma. Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

Citation

Shuanglan Xu, Zi Chen, Linyang Ge, Chenhui Ma, Quan He, Weihua Liu, Liuchao Zhang, Linfu Zhou. Identification of potential biomarkers and pathogenesis in neutrophil-predominant severe asthma: A comprehensive bioinformatics analysis. Medicine. 2022 Sep 23;101(38):e30661