Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease with limited treatment options of corticosteroids, sinus surgery, or both. CRSwNP is frequently associated with allergic rhinitis and asthma, but the molecular mechanisms underlying CRSwNP inflammation are not completely understood. We obtained four gene expression profiles (GSE136825, GSE36830, GSE23552, and GSE72713) from four Gene Expression Omnibus (GEO), which collectively included 65 nasal polyp samples from CRSwNP patients and 54 nasal mucosal samples from healthy controls. Using an integrated analysis approach, we identified 76 co-differentially expressed genes (co-DEGs, including 45 upregulated and 31 downregulated) in CRSwNP patients compared with the healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified the terms including immune effector process, leukocyte migration, regulation of the inflammatory response, Staphylococcus aureus infection, and cytokine-cytokine receptor interaction. protein-protein interaction (PPI) network analysis and real-time quantitative PCR (RT-qPCR) showed that 7 genes might be crucial in CRSwNP pathogenesis. Repurposing drug candidates (Alfadolone, Hydralazine, SC-560, Iopamidol, Iloprost, etc) for CRSwNP treatment were identified from the Connectivity Map (CMap) database. Our results suggest multiple molecular mechanisms, diagnostic biomarkers, potential therapeutic targets, and new repurposing drug candidates for CRSwNP treatment.
Highlights
Chronic rhinosinusitis (CRS) is a common chronic heterogeneous nasal inflammatory disease that is associated with significant morbidity and a decreased quality of life
To avoid a high proportion of false positives in an individual dataset, multiple-dataset integration was necessary for obtaining reliable results to further investigate the complex molecular mechanisms of CRS with nasal polyps (CRSwNP)
A cluster heatmap was used to visualize the changes in up- and downregulated genes among 76 co-differentially expressed genes (DEGs) (Figure 2C), and details of the 76 co-differentially expressed genes (co-DEGs) are shown in Supplementary Table 1
Summary
Chronic rhinosinusitis (CRS) is a common chronic heterogeneous nasal inflammatory disease that is associated with significant morbidity and a decreased quality of life. CRSwNP can be classified into 2 distinct immunohistological subtypes based on eosinophil infiltration, eosinophilic CRSwNP (Eos CRSwNP) and noneosinophilic CRSwNP (non-eos CRSwNP) (Cao et al, 2009). Eos CRSwNP demonstrates Th2 inflammation skewed with a relatively high recurrence and asthma comorbidity rate, while non-eos CRSwNP is characterized by a Th1 or Th17 response and a lower recurrence and asthma comorbidity rate (Zhang et al, 2008; Cao et al, 2009). The inflammatory mechanisms underlying CRSwNP are not completely defined. In this regard, biomarkers that precisely indicate the development and progression of CRSwNP need to be further investigated to develop novel clinical strategies for CRSwNP treatment
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