Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma

Abstract

Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function improvements in response to inhaled corticosteroids (ICSs). A total of 47 patients with asthma were recruited and classified as good responders (GRs) and poor responders (PRs) based on their responses to ICSs. Genome-wide gene expression was measured using peripheral blood mononuclear cells obtained in a stable state. We used Passing Attributes between Networks for Data Assimilations to construct the gene regulatory networks associated with GRs and PRs to ICSs. We identified the top-10 TFs that showed large differences in high-confidence edges between the GR and PR aggregate networks. These top-10 TFs and their differentially-connected genes in the PR and GR aggregate networks were significantly enriched in distinct biological pathways, such as TGF-beta signaling, cell cycle, and IL-4 and IL-13 signaling pathways. We identified multiple TFs and related biological pathways influencing ICS responses in asthma. Our results provide potential targets to overcome insensitivity to corticosteroids in patients with asthma.