Bioinformatics Analysis of Gene Expression Profiles Reveals Potential Molecular Mechanisms of Chronic Rhinosinusitis with Nasal Polyps

【Abstract】\nObjective: This study aimed to explore the potential pathogenesis and biological markers of chronic rhinosinusitis with nasal polyps (CRSwNP) by data mining of CRSwNP nasal polyp tissue and healthy controls using bioinformatics techniques.\nMethods: GSE36830, GSE23552, and GSE194282 datasets were downloaded from the GEO database. Differential gene expression analysis was conducted using R language to identify differentially expressed genes (DEGs) between the healthy control group and the disease group. Gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on the DEGs. The DEGs were used to construct a protein-protein interaction network (PPI) using STRING platform and Cytoscape software, and key genes were extracted using the cytoHubba plugin. The results of bioinformatics analysis were validated by immunohistochemistry and Western blot. Finally, potential small molecule drugs were screened using the Cmap database.\nResults: A total of 155 DEGs (101 upregulated genes and 54 downregulated genes) were identified between the CRSwNP nasal polyp group and the healthy control group (P < 0.05). Functional enrichment analysis showed that upregulated genes were mainly enriched in inflammation response and immune regulation, while downregulated genes were mainly enriched in cell growth and epithelial morphology. Five key genes potentially involved in the regulation of CRSwNP were identified using cytoHubba: ITGAM, CD86, TYROBP, CYBB, and CSF1R. Experimental validation was conducted on the less studied CYBB and CSF1R genes. Immunohistochemistry results showed that in the CRSwNP group, CYBB and CSF1R were mainly expressed in epithelial cells, with positive expression appearing brown or brownish-yellow, mainly distributed in... In the healthy control group, CYBB and CSF1R were minimally expressed in epithelial cells, with faint yellow staining, and the staining intensity was significantly weaker than that in the CRSwNP group. Western blot results demonstrated clear immune-reactive bands of CYBB and CSF1R in the mucosal tissue of the disease group at kDa and kDa, while the immune-reactive bands in the healthy control group were significantly weaker than those in the CRSwNP group. Semi-quantitative analysis of the gray values of immune-reactive bands using Image J software showed that the gray values of CYBB and CSF1R bands in the CRSwNP group were significantly higher than those in the healthy control group, and the difference was statistically significant (P < 0.05).\nConclusion: Five hub genes (ITGAM, CD86, TYROBP, CYBB, and CSF1R) were identified, among which CYBB and CSF1R were key genes for further investigation. These hub genes may be involved in the occurrence and development of chronic rhinosinusitis with nasal polyps. Immune dysfunction and inflammation response may be contributing factors to nasal mucosal or epithelial damage. The results of this study provide preliminary insights into the potential molecular mechanisms of CRSwNP.\n\nKeywords: chronic rhinosinusitis with nasal polyps; key genes; bioinformatics; molecular mechanisms