Macroarray expression analysis of cytokines and prostaglandin metabolism-related genes in chronic rhinosinusitis

Aiko Oka; Kengo Kanai; Takaya Higaki; Seiichiro Makihara; Yohei Noda; Shin Kariya; Mizuo Ando; Wataru Nishimura; Mitsuhiro Okano

doi:10.1016/j.jacig.2023.100123

Macroarray expression analysis of cytokines and prostaglandin metabolism-related genes in chronic rhinosinusitis

J Allergy Clin Immunol Glob. 2023 Jun 3;2(3):100123. doi: 10.1016/j.jacig.2023.100123. eCollection 2023 Aug.

Authors

Aiko Oka¹, Kengo Kanai¹, Takaya Higaki², Seiichiro Makihara², Yohei Noda², Shin Kariya³, Mizuo Ando², Wataru Nishimura⁴, Mitsuhiro Okano¹

Affiliations

¹ Department of Otorhinolaryngology, International University of Health and Welfare School of Medicine, Narita, Japan.
² Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
³ Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School, Okayama, Japan.
⁴ Department of Molecular Biology, International University of Health and Welfare School of Medicine, Narita, Japan.

Abstract

Background: Chronic rhinosinusitis (CRS) can be divided into endotypes by functional or pathophysiologic findings.

Objective: The aim of this study was to analyze the expression of cytokines, prostaglandin (PG) synthases, and their receptors related to the pathogenesis of CRS, especially those contributing to nasal polyp (NP) formation.

Methods: NPs and uncinate tissue (UT) samples were collected from 90 patients who underwent endoscopic sinus surgery. They included 75 patients with CRS (including 45 with eosinophilic CRS [eCRS] and 30 with non-eCRS) and 15 patients without CRS. A total of 30 genes were selected for our original DNA array plate to analyze the levels of expression of 10 cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-13, IL-17A, IL-22, IL-25, IL-33, and TSLP), 4 prostaglandin synthases (prostaglandin D₂ [PGD₂] synthase, prostaglandin E₂ synthase, COX-1, and COX-2), and their 16 receptors. Clustering analysis was performed according to the expression results, and clinical findings of patients from each cluster were investigated.

Results: The samples could be divided into 3 clusters. Cluster 1 showed elevated levels of expression of IL4, IL5, IL13, TSLP, IL1RL1 (ST2 [an IL-33 receptor]), HPGDS, and GPR44 (CRTH2, a PGD₂ receptor); cluster 2 showed elevated levels of expression of IL17A and PTGES; and cluster 3 showed an elevated level of expression of IL25. Regarding clinical features, the main characteristics of each cluster were as follows: NPs from patients with eCRS for cluster 1, NPs and/or UT samples from patients with non-eCRS for cluster 2, and UTs from patients with non-CRS for cluster 3.

Conclusion: The results suggest that there are associations between type 2 inflammation/PGD₂ and eCRS and also between type 3 inflammation/prostaglandin E₂ and non-eCRS.

Keywords: Chronic rhinosinusitis; clustering analysis; cytokine; endotyping; gene expression; personalized medicine; prostaglandin; receptor.