Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with relatively easy recurrence. However, the precise molecular mechanisms of this disease are poorly known. Based on gene sequencing data obtained from the Gene Expression Omnibus (GEO) database, we constructed coexpression networks by weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core gene of pathogenesis, CRSwNP, was screened by protein-protein interaction data (PPI) from the HPRD database. Unsupervised clustering was applied to screen hub genes related to the phenotype of CRSwNP. Blue and turquoise modules were found to be most significantly related to the pathogenicity of CRSwNP. Functional enrichment analysis showed that cell proliferation in the blue modules, the apoptotic process in the turquoise module, and the cancer pathway in both modules were mostly significantly correlated with the development of CRSwNP. The noncoding RNAs (long noncoding RNA and microRNA) and the top 10 core genes in each module were found to be associated with the pathogenesis of CRSwNP. A total of nine hub genes were identified to be related to the CRSwNP phenotype. By qRT-PCR analysis, AKT1, CDH1, PIK3R1, CBL, LRP1, MALAT1, and XIST were proven to be associated with the pathogenesis of CRSwNP. AGR2, FAM3D, PIP, DSE, and TMC were identified to be related to the CRSwNP phenotype. Further exploration of these genes will reveal more important information about the mechanisms of CRSwNP.
Highlights
Chronic rhinosinusitis (CRS) is highly prevalent, affecting approximately 11% to 15% of the adult population [1, 2] and contributing to annual direct healthcare costs of $11 billion [3]
GSE107624 consists of 21 nasal polyps (NPs) samples and 21 normal control samples, and its platform is the [HG-U219] Affymetrix Human Genome U219 Array. e samples were isolated from NPs or control nasal mucosa and cultured and differentiated at the air-liquid interface (ALI) cell culture system. e information in both datasets is summarized in Table 1. e original data were processed using R packets affy_1.62.0 and annotated to form an expression matrix, and the probe was matched to its gene symbols
A total of 778 differentially expressed genes (Figure 1(a)) were screened in GSE107624, and 54 DEGs (Figure 1(b)) were screened in GSE36830. |log 2 fold change| > 2 and a false discovery rate (FDR) adjusted to P < 0.05 were considered DEGs. en, the two groups of DEGs were compared with the NP-related genes in the public database (NCBI and OMIM), and a total of 1063 potential genes (Figure 1(c)) of Chronic rhinosinusitis with nasal polyps (CRSwNP) were obtained
Summary
Chronic rhinosinusitis (CRS) is highly prevalent, affecting approximately 11% to 15% of the adult population [1, 2] and contributing to annual direct healthcare costs of $11 billion [3]. CRS is a heterogeneous group of diseases with common symptoms and clinical findings, but different pathophysiologies. CRSwNP is a chronic inflammatory disease that is characterized by inflammation of the nasal mucosa, nasal obstruction, and the growth of CRSwNP [3]. Because CRSwNP is prone to relapse and brings great pain to patients, it is urgent to understand its molecular mechanism, as well as to promote research on related drugs. Some genes such as SRC [5], SMAD3 [6], and CDH1 [7] have been found to play roles in the pathogenesis of CRSwNP.
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