Comparing Protein and Gene Expression Signature between Nasal Polyps and Nasal Fluids in Chronic Rhinosinusitis

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. Method: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman's analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. Results: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (rho > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (rho = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (rho = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (rho > 0.68, p < 0.05 for all). Conclusion: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient.

Automated summary

This study compared the protein and mRNA inflammation signatures between nasal polyps (NPs) and nasal fluids (NFs) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The results showed that the concentration of cytokines was higher in NFs collected using NFAD compared to PVA sponge, and these cytokine levels were significantly associated with NPs. Differentially expressed proteins between NFs and NPs were significantly correlated in the eosinophilic CRSwNP subgroup. There was also a significant correlation between gene and protein expression. The levels of PDL2 in NFs were positively correlated with ECRSwNP postoperative recurrence, nasal VAS, and SNOT-22 scores.