Gene expression data analysis identifies multiple deregulated pathways in patients with asthma

Reem H Alrashoudi, Isabel J Crane, Heather M Wilson, Monther Al-Alwan, Nehad M Alajez

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Abstract

Asthma is a chronic inflammatory disorder associated with airway hyperesponsiveness. 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. Normals and mild asthmatic patients clustered separately from the severe asthma group, suggesting substantial progression-related changes in gene expression. Pathway analysis of upregulated severe asthma-related genes identified multiple cellular processes, such as polymorphism, T cell development, and transforming growth factor beta (TGFβ) signaling. Comparing gene expression profiles of bronchoalveolar lavage (BAL) cells in response to corticosteroid treatment, showed substantial reductions in genes related to the inflammatory response, including tumor necrosis factor (TNF) signaling in the corticosteroid sensitive vs 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.

Original languageEnglish
Article numberBSR20180548
JournalBioscience Reports
Volume38
Issue number6
Early online date23 Jul 2018
DOIs
Publication statusPublished - Dec 2018

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Gene expression
Adrenal Cortex Hormones
Asthma
Gene Expression
Genes
T-cells
Polymorphism
Transcriptome
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Bronchoalveolar Lavage
Interleukin-2
Therapeutics

Keywords

  • Journal Article

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Gene expression data analysis identifies multiple deregulated pathways in patients with asthma. / Alrashoudi, Reem H; Crane, Isabel J; Wilson, Heather M; Al-Alwan, Monther; Alajez, Nehad M.

In: Bioscience Reports, Vol. 38, No. 6, BSR20180548, 12.2018.

Research output: Contribution to journalArticle

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