TY - JOUR T1 - Whole-transcriptome sequencing reveals heightened inflammation and defective host defence responses in chronic rhinosinusitis with nasal polyps JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00732-2019 VL - 54 IS - 5 SP - 1900732 AU - Yang Peng AU - Xiao-Xue Zi AU - Teng-Fei Tian AU - Bernett Lee AU - Josephine Lum AU - See Aik Tang AU - Kai Sen Tan AU - Qian-Hui Qiu AU - Jing Ye AU - Li Shi AU - Wei-Jie Guan AU - Anand Kumar Andiappan AU - De Yun Wang Y1 - 2019/11/01 UR - http://erj.ersjournals.com/content/54/5/1900732.abstract N2 - Introduction The 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.Methods We 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.Results Principal 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.Conclusions Gene 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.Whole-transcriptome sequencing shows gene signatures associated with interferon signalling response and host defence are implicated in chronic rhinosinusitis with nasal polyps, opening up new opportunities for therapeutic interventions http://bit.ly/2KyF3dT ER -