Pathways analysis of molecular markers in chronic sinusitis with polyps.

OBJECTIVE

To perform a comprehensive molecular pathways analysis of genes identified through genome-wide expression profiling and the published literature for chronic sinusitis with polyps.

STUDY DESIGN

Molecular pathways analysis.

SETTING

Academic medical center.

METHODS

A molecular pathways analysis of gene biomarkers discovered through hypothesis-driven and high-throughput molecular studies was performed. Genes identified with a PubMed literature search were analyzed with Ingenuity Pathways Analysis software to identify central molecules implicated in the pathogenesis of chronic sinusitis with polyps. The central pathways were then compared with those identified through genome-wide expression profiling of ethmoid polyps.

RESULTS

A total of 97 molecules were investigated with Ingenuity Pathways Analysis based on 55 studies that evaluated differences in gene expression (39), genetic variation (12), or proteomics (4). The analysis revealed 9 statistically significant molecular networks containing central nodes that included transcription factors, protein kinases, cytokines, and growth factors/receptors. The highest scoring networks implicated nuclear factor kappa-B, tumor necrosis factor, and mitogen-activated protein kinases. The majority of pathways in the literature review analysis overlapped with those identified through a single genome-wide expression study.

CONCLUSIONS

Chronic sinusitis with polyps is a complex disease with suspected contribution of multiple genetic and environmental factors. The search for causative genes has led to the discovery of numerous candidates. Pathways analysis applied to these candidate genes identified common central molecules that are likely to be key mediators of the disease process. Novel therapies targeting these molecules may be applicable for the treatment of chronic sinusitis with polyps.