Whole-transcriptome sequencing reveals heightened inflammation and defective host defence responses in chronic rhinosinusitis with nasal polyps

Abstract

IntroductionThe pathways underlying chronic rhinosinusitis with nasal polyps (CRSwNP) are unclear. We conducted genome-wide gene expression analysis to determine pathways and candidate gene sets associated with CRSwNP.MethodsWe performed whole-transcriptome RNA sequencing on 42 polyp (CRSwNP-NP) and 33 paired nonpolyp inferior turbinate (CRSwNP-IT) tissues from patients with CRSwNP and 28 inferior turbinate samples from non-CRS controls (CS-IT). We analysed the differentially expressed genes (DEGs) and the gene sets that were enriched in functional pathways.ResultsPrincipal component-informed analysis revealed cilium function and immune regulation as the two main Gene Ontology (GO) categories differentiating CRSwNP patients from controls. We detected 6182 and 1592 DEGs between CRSwNP-NP versus CS-IT and between CRSwNP-NP versus CRSwNP-IT tissues, respectively. Atopy status did not have a major impact on gene expression in various tissues. GO analysis on these DEGs implicated extracellular matrix (ECM) disassembly, O-glycan processing, angiogenesis and host viral response in CRSwNP pathogenesis. Ingenuity Pathway Analysis identified significant enrichment of type 1 interferon signalling and axonal guidance canonical pathways, angiogenesis, and collagen and fibrotic changes in CRSwNP (CRSwNP-NP and CRSwNP-IT) tissues compared with CS-IT. Finally, gene set enrichment analysis implicated sets of genes co-regulated in processes associated with inflammatory response and aberrant cell differentiation in polyp formation.ConclusionsGene signatures involved in defective host defences (including cilia dysfunction and immune dysregulation), inflammation and abnormal metabolism of ECM are implicated in CRSwNP. Functional validation of these gene expression patterns will open opportunities for CRSwNP therapeutic interventions such as biologics and immunomodulators.

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

“…Our ndings for RNA sequencing provides valuable information for exploring the general molecular mechanisms underlying the pathogenesis of CRSwNP. Similar to the ndings of Peng and colleagues [40], our study has demonstrated that regardless of the subtypes of CRSwNP, genes and pathways that most likely contribute to the pathogenesis of CRSwNP, appear to be mainly associated with cytokine and chemokine signalling pathway, staphylococcus aureus infection, eicosanoid metabolism and cell adhesion molecules. In this respect, the well-known genes or biomarkers closely related to CRSwNP; for example CLC, POSTN, CCL18, IL13, TSLP and BPIFA1; were also identi ed as the top DE-mRNAs in both CRSwNP-alone and CRSwNP+AS groups.…”

Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma

“…Our findings for RNA sequencing provides valuable information for exploring the general molecular mechanisms underlying the pathogenesis of CRSwNP. Similar to the findings of Peng and colleagues [40], our study has demonstrated that regardless of the subtypes of CRSwNP, genes and pathways that most likely contribute to the pathogenesis of CRSwNP, appear to be mainly associated with cytokine and chemokine signalling pathway, and yellow module (f) visualized by cytoscape network. mRNAs or lncRNAs with high connectivity and edges with weight above a threshold of 0.1 were identified as hub genes.…”

Distinct Type 2-high Inflammation Associated Molecular Phenotypes of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

“…Our RNA sequencing data provides valuable information for exploring the general molecular mechanisms underlying the pathogenesis of CRSwNP. Regardless of the subtypes of CRSwNP, genes and pathways that most likely contribute to the pathogenesis of CRSwNP might be mainly associated with cytokine and chemokine signaling pathway, staphylococcus aureus infection, eicosanoid metabolism and cell adhesion molecules, which were similar to Peng's findings [28]. The well-known genes or biomarkers closely related to CRSwNP such as CLC, POSTN, CCL18, IL13, TSLP and BPIFA1…”