Multi-scale transcriptomic integration reveals epithelial state heterogeneity and remodeling-associated transcriptomic clusters in chronic rhinosinusitis with nasal polyps.

BACKGROUND

Chronic rhinosinusitis with nasal polyps (CRSwNP) involves persistent mucosal inflammation and epithelial remodeling, yet the molecular mechanisms driving epithelial dysfunction remain unclear.

METHODS

Single-cell and bulk RNA sequencing data were integrated to characterize the cellular composition, gene expression patterns, and pathway activities in CRSwNP. Single-cell clustering, pseudotime analysis, and cell annotation were performed to define epithelial cell subsets. Bulk transcriptomic data underwent differential expression, enrichment, and pathway analysis. Gene set variation analysis (GSVA) and LASSO regression were applied to construct a pathway-based signature score, followed by consensus clustering for transcriptomic cluster identification.

RESULTS

Epithelial cells exhibited clear heterogeneity, with basal, secretory, and ciliated subsets forming a continuous differentiation trajectory. Upregulated pathways included extracellular matrix organization, PI3K-Akt signaling, and epithelial-mesenchymal transition, while interferon and NF-κB signaling were suppressed. Pathway-based modeling identified two internally consistent transcriptomic clusters: one dominated by epithelial barrier and ciliary activity, and another characterized by extracellular remodeling and IL-13/TGF-β signaling.

CONCLUSIONS

This multi-scale transcriptomic analysis highlights epithelial state heterogeneity and extracellular remodeling as potential molecular features of CRSwNP and proposes an exploratory transcriptomic stratification that warrants further validation in independent cohorts.