Gene expression data analysis identifies multiple deregulated pathways in patients with asthma
Gene expression data analysis identifies multiple deregulated pathways in patients with asthma
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DOI：
10.1042/bsr20180548
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发表时间：
2018-12-21
影响因子：
4
通讯作者：
Alajez, Nehad M.
中科院分区：
文献类型：
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作者：
Alrashoudi, Reem H.;Crane, Isabel J.;Alajez, Nehad M.
哮喘是一种与气道高反应性相关的慢性炎症性疾病。尽管许多研究在分子水平上调查了哮喘，但与哮喘严重程度或对皮质类固醇反应相关的分子免疫特征仍不清楚。本研究整合了基因表达综合库中的四个哮喘相关基因表达数据集，并确定了与哮喘发展、严重程度或治疗反应相关的免疫基因特征。正常和轻度哮喘患者与重度哮喘组分开，表明基因表达发生了与进展相关的重大变化。对上调的严重哮喘相关基因的通路分析发现了多种细胞过程，例如多态性、T 细胞发育和转化生长因子-β 信号传导。比较皮质类固醇治疗后支气管肺泡灌洗细胞的基因表达谱，发现与炎症反应相关的基因大幅减少，包括皮质类固醇敏感患者与耐药患者中的肿瘤坏死因子信号转导，这表明对皮质类固醇的免疫反应有缺陷。这些数据强调了哮喘的多因素性质，但显示与当前研究中不同数据集的基因表达谱没有显着重叠。所提出的概况表明，参与哮喘进展的基因与参与皮质类固醇反应的基因不同，这可能会影响不同哮喘患者群体的临床管理。
Asthma is a chronic inflammatory disorder associated with airway hyper-responsiveness. Although a number of studies have investigated asthma at the molecular level, the molecular immune signatures associated with asthma severity or with the response to corticosteroids are still being unraveled. The present study integrated four asthma-related gene expression datasets from the Gene Expression Omnibus and identified immune-gene signatures associated with asthma development, severity, or response to treatment. Normal and mild asthmatic patients clustered separately from the severe asthma group, suggesting substantial progression-related changes in gene expression. Pathway analysis of up-regulated severe asthma-related genes identified multiple cellular processes, such as polymorphism, T-cell development, and transforming growth factor-beta signaling. Comparing gene expression profiles of bronchoalveolar lavage cells in response to corticosteroid treatment, showed substantial reductions in genes related to the inflammatory response, including tumor necrosis factor signaling in the corticosteroid sensitive versus resistant patients, suggesting a defective immune response to corticosteroids. The data highlight the multifactorial nature of asthma, but revealed no significant overlap with the gene expression profiles from different datasets interrogated in current studies. The presented profile suggests that genes involved in asthma progression are different from those involved in the response to corticosteroids and this could affect the clinical management of different groups of patients with asthma.