Research Assistant Professor Northwestern Univ. Feinberg Sch. of Med. Chicago, Illinois, United States
Introduction/Rationale: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the upper airway, yet the molecular pathways underpinning nasal polyps (NP) immunopathogenesis and endotypic diversity remain incompletely understood.
Methods: We profiled tissue bulk RNA-seq from 88 NP and 317 ethmoids from CRS. Weighted gene co‑expression network analysis (WGCNA) identified NP-associated modules, followed by differential expression and functional enrichment.
Results: WGCNA revealed six NP-associated modules compared to ethmoids, and the blue module was most NP-associated. Blue-module pathways were enriched for cytokine/chemokine receptor signaling, hematopoietic regulation, and immune differentiation, consistent with type 2 and mixed inflammatory programs. GSEA further highlighted cell adhesion/activation, leukocyte and mononuclear cell migration, actin filament organization, and GPCR signaling, supporting coordinated immune trafficking and epithelial–immune crosstalk in NP progression. Blue-module PPI mapping converged on SYK/BTK-centered B cell/Fc receptor signaling, integrin–ICAM1 adhesion/migration, and epithelial cytoskeletal remodeling. In addition, this module showed the strongest link to radiographic severity, correlating with Lund-Mackay (r=0.60, p< 0.001), indicating that the coordinated immune gene expression best predicts disease burden.
Conclusion: Bulk transcriptomic network analysis identifies a dominant NP immune-activation program that reflects type 2 and mixed type 2/3 inflammation and shows the strongest association with radiographic disease severity. This module-level signal better captures disease burden than individual biomarkers and underscores coordinated epithelial–immune interactions—highlighting SYK/BTK signaling and integrin/ICAM1-mediated adhesion/migration alongside epithelial remodeling—as key drivers of polyp progression.
