School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, #44 West Wenhua Road, Jinan, 250012, China.
BMC Med Genomics. 2021 Feb 18;14(1):51. doi: 10.1186/s12920-021-00892-4.
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.
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.
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.
Our results identified biomarkers and characterized potential pathogenesis of severe asthma, providing insight into treatment targets and prognostic markers.
重度哮喘是一种异质性炎症性疾病。为了更深入地了解分子机制和生物标志物，精准免疫疗法在重度哮喘患者中的应用不断增加。本研究旨在确定决定哮喘严重程度的潜在机制和关键基因。
根据轻度和重度哮喘患者的支气管上皮刷检标本，鉴定差异表达基因（DEGs）。然后，采用加权基因共表达网络分析（WGCNA）来鉴定与哮喘严重程度最显著相关的基因网络和模块。此外，还进行了关键基因筛选和功能富集分析。采用另一个数据集进行复制来验证关键基因。
对 14 例轻度和 11 例重度哮喘患者的 DEGs 进行了 WGCNA。鉴定出 6 个与哮喘严重程度相关的模块。其中 3 个模块与哮喘严重程度呈正相关（P<0.001），并包含在重度哮喘患者中上调的基因。功能富集分析表明，最显著模块中的基因主要富集于中性粒细胞的激活和脱颗粒，以及细胞因子受体相互作用。关键基因包括 CXCR1、CXCR2、CCR1、CCR7、TLR2、FPR1、FCGR3B、FCGR2A、ITGAM 和 PLEK；CXCR1、CXCR2 和 TLR2 在验证数据集中与哮喘严重程度显著相关。十个关键基因的组合在区分重度和轻中度哮喘患者方面具有中等能力。
我们的研究结果确定了生物标志物，并描述了重度哮喘的潜在发病机制，为治疗靶点和预后标志物提供了新的见解。
