[Transcriptomic expression profile characteristics of nasal polyps with uncontrolled disease after endoscopic sinus...

Objective: To investigate the transcriptomic signature of refractory nasal polyps (NP) after endoscopic sinus surgery. Methods: Tissue samples were collected from 36 patients with NP who underwent endoscopic sinus surgery at the Seventh Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021. Raw sequencing data of normal nasal mucosa samples were downloaded from publicly available GEO database (Accession Number: GSE136825). Differential expression genes (DEGs) and Gene Ontology (GO) enrichment analysis were conducted to analyze the differences between refractory NP and normal controls, as well as among refractory, controlled, and partially controlled NP. Hierarchical clustering method was employed to analyze the inflammatory endotypes of NP. Weighted Gene Co-expression Network Analysis (WGCNA) and STRING database were used in combination with Cytoscape software to identify the characteristic transcriptional expression profiles of refractory NP. R software (version 4.3.1) was used for statistical analysis. Results: Refractory NP patients had significantly higher asthma comorbidity rates than controlled/partially controlled groups (P<0.05). The numbers and percentages of peripheral blood and tissue eosinophilic granulocytes were significantly higher in the refractory subgroup than in the other two subgroups (P<0.05). Compared to normal mucosa, controlled and partially controlled NP groups, 27 genes were consistently upregulated in refractory NP. Hierarchical cluster analysis showed that the refractory NP exhibited a mixed endotype dominated by type 2 inflammation with co-existing type 1 features. Differential genes were enriched in extracellular matrix organization, leukocyte activation, cytokine receptor activation, cystatin-mediated protease inhibition, granule exocytosis, and olfactory nerve development regulation. Further WGCNA analysis and protein-protein interaction network identified 33 hub genes represented by ITGAM, NCF1, NCF2, CD1C, PTAFR, CLEC10A, SIRPA, TREM2, ALOX5AP, PTGDR2 (officially PTGDR), F13A1, DUOX2, NOS2, CTSG, and SALL1. Conclusion: This study reveals the distinctive transcriptional signature of refractory NP through transcriptomic methods, providing novel research avenues and therapeutic targets for the treatment of refractory NP after surgery.