Author:
Zhang Zeyi,Wang Jingjing,Chen Ou
Abstract
Abstract
Background
Severe asthma is a heterogeneous inflammatory disease. The increase in precise immunotherapy for severe asthmatics requires a greater understanding of molecular mechanisms and biomarkers. In this study, we aimed to identify the underlying mechanisms and hub genes that determine asthma severity.
Methods
Differentially expressed genes (DEGs) were identified based on bronchial epithelial brushings from mild and severe asthmatics. Then, weighted gene coexpression network analysis (WGCNA) was used to identify gene networks and the module most significantly associated with asthma severity. Furthermore, hub gene screening and functional enrichment analysis were performed. Replication with another dataset was conducted to validate the hub genes.
Results
DEGs from 14 mild and 11 severe asthmatics were subjected to WGCNA. Six modules associated with asthma severity were identified. Three modules were positively correlated (P < 0.001) with asthma severity and contained genes that were upregulated in severe asthmatics. Functional enrichment analysis showed that genes in the most significant module were mainly enriched in neutrophil activation and degranulation, and cytokine receptor interaction. Hub genes included CXCR1, CXCR2, CCR1, CCR7, TLR2, FPR1, FCGR3B, FCGR2A, ITGAM, and PLEK; CXCR1, CXCR2, and TLR2 were significantly related to asthma severity in the validation dataset. The combination of ten hub genes exhibited a moderate ability to distinguish between severe and mild-moderate asthmatics.
Conclusion
Our results identified biomarkers and characterized potential pathogenesis of severe asthma, providing insight into treatment targets and prognostic markers.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Cited by
14 articles.
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