Comprehensive profiling of the heterogeneity of molecular endotypic traits in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common clinical disease with molecular endotypes. In the present study, we performed a comprehensive transcriptomic profiling to investigate the heterogeneity of endotypes in CRS with nasal polyps (CRSwNP). The GSE23552 dataset, which includes microarray, was acquired from the Gene Expression Omnibus database. Additionally, surgical specimens were collected at Gunma University Hospital, and reverse transcription-quantitative PCR was performed. We performed gene expression analysis, Gene Set Enrichment Analysis (GSEA), deconvolution analysis, and hierarchical clustering of samples. Gene expression analysis and GSEA revealed that type 1, type 2, and Treg-related responses, were upregulated in nasal polyp tissues when compared with those in controls. Deconvolution analysis indicated the enrichment of type 1-related cells and generation of memory T cells. Furthermore, nasal polyps exhibited higher expression of effector function- and immune checkpoint-related genes than controls. In addition, hierarchical clustering revealed the heterogeneity in patients with type 2-inflamed CRSwNP. Notably, type 1 and type 2 scores correlated with the duration from surgery to biopharmaceuticals initiation. In conclusion, our study demonstrated the heterogeneity of molecular endotypes in CRSwNP. Further characterisation and stratification are required to develop a new endotype-based precision medicine for patients with CRS.