Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non-eosinophilic chronic rhinosinusitis

Int Forum Allergy Rhinol. 2018 May;8(5):592-604. doi: 10.1002/alr.22083. Epub 2018 Jan 16.

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2 phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue eosinophilia and easily recurrent, is distinguished from other non-eosinophilic CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear.

Methods: Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis [IPA]) were used to interrogate the data sets.

Results: Hierarchical clustering and principal component analysis (PCA) collectively showed that ECRSwNP and NECRSwNP had distinct gene expression patterns. Of note, these genes could be divided into 8 distinctive clusters having different expression patterns and functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis-related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in NECRSwNP.

Conclusion: These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.

Keywords: chronic rhinosinusitis; gene expression patterns; microarray analysis; nasal polyps; pathway analysis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Cell Cycle / genetics
  • Chronic Disease
  • Cytokines / genetics
  • Cytokines / metabolism
  • Eosinophils / physiology*
  • Female
  • Gene Regulatory Networks
  • Humans
  • Male
  • Middle Aged
  • Nasal Polyps / diagnosis
  • Nasal Polyps / genetics*
  • Paranasal Sinuses / pathology*
  • Rhinitis / diagnosis
  • Rhinitis / genetics*
  • Sinusitis / diagnosis
  • Sinusitis / genetics*
  • Th2 Cells / immunology
  • Transcriptome

Substances

  • Biomarkers
  • Cytokines