Bioinformatics analysis and verification of key candidate genes influencing the pathogenesis of chronic rhinosinusitis with nasal polyps.

OBJECTIVES

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a prominent public health issue. Furthermore, the prognosis of eosinophilic CRSwNP is poor, with a high recurrence rate. The underlying molecular mechanisms of eosinophilic CRSwNP remain unclear. Therefore, in this study, we sought to determine the crucial genes underlying eosinophil infiltration in eosinophilic CRSwNP pathogenesis.

METHODS

We used the Gene Expression Omnibus database (GEO) (GSE36830 and GSE23552 datasets) to mine gene expression profiles of CRSwNP patients and normal subjects. Differentially expressed genes (DEGs) between normal and CRSwNP tissues were identified and subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Co-expression networks were established using a weighted gene co-expression network analysis (WGCNA) and single-sample gene set enrichment analysis (GSEA). Protein-protein interaction networks were developed to detect functional protein modules. Based on the common DEGs, candidate miRNAs and related lncRNAs were predicted using the mirTarBase and StarBase databases. Finally, we generated immune cell subtypes of CRSwNP.

RESULTS

A total of 146 DEGs were identified. Of these, 131 genes were upregulated, whereas 15 were downregulated. GO analysis indicated that DEGs primarily participated in leukocyte chemotaxis and migration as well as cell chemotaxis. KEGG pathway analysis suggested that DEGs participated in the interactions between cytokines and viral proteins, osteoclast differentiation, and cytokine-cytokine receptor interactions. Real-time quantitative polymerase chain reaction analysis showed that and expression levels were significantly upregulated in nasal polyps, whereas expression levels were significantly downregulated.

CONCLUSIONS

The candidate genes identified in this study may influence the activation and accumulation of eosinophils, cell chemotaxis, and inflammatory responses, thereby potentially representing molecular targets for future studies of CRSwNP.