Transcriptomic and Lipidomic Profiles in Nasal Polyps of Glucocorticoid Responders and Non-Responders: Before and After Treatment

Abstract

Background: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and mechanisms underlying different responses to systemic glucocorticoids (GC) remain unclear. The major aim of this study was to explore the transcriptomic and oxidative lipidomic signatures and the effects of GC in patients with different clinical responses.Methods: Nasal polyp biopsies were obtained before and after 14-day oral GC treatment from 16 patients with CRSwNP, and normal nasal mucosa specimens were collected from 12 control subjects. RNA sequencing and oxidative lipidomics were performed, and differential gene expression analysis was conducted in the Responder and Non-responder groups at baseline and after treatment.Results: In the Responder group, GC significantly improved clinical symptoms and reduced tissue eosinophil infiltration. Meanwhile, GC led to a pronounced transcriptomic reversion with robust suppression of inflammatory responses and abnormal metabolism of extracellular matrix, as well as restoration of cilia function. However, non-responders were mainly characterized by epithelial hyperplasia and keratinization, with much less transcriptomic improvement after GC treatment. Higher expression of type 2 inflammatory molecules (CCL13, IGHE, CCL18, CCL23, CCR3, and CLC) with lower levels of LACRT, PPDPFL, DES, C6, MUC5B, and SCGB3A1 were related to a stronger clinical response to GC. Besides decreased prostaglandins and increased leukotrienes, increased dysregulation in other oxylipid mediators derived from polyunsaturated fatty acids was determined in nasal polyps, which was ameliorated by GC treatment.Conclusion: Systemic GC exert anti-inflammatory effects, improve tissue remodeling, restore cilia function, and ameliorate dysregulation of oxylipid mediator pathway in CRSwNP. GC-responders exhibited different transcriptomic signatures from non-responders.

Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

“…Production of CCL26 is induced by IL4/13 in epithelial cells [ 16 ], and CCL26 induces not only eosinophil infiltration but also NK cell migration, which contributes to trafficking NK cells to the allergic upper airway mediated by CX3CL1 and the tyrosine kinase pathway [ 17 ]. Higher expression of type 2 inflammatory molecules ( CCL13, IGHE, CCL18, CCL23, CCR3, and CLC ) along with lower levels of LACRT, PPDPFL, DES, C6, MUC5B, and SCGB3A1 are related to a stronger clinical response to glucocorticoids [ 18 ]. In terms of the above-mentioned evidence, these differences would explain the difference of each phenotype as to whether they mainly have type 2 inflammation or not.…”

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”