TY - JOUR T1 - Whole-transcriptome sequencing reveals heightened inflammation and defective host-defense responses in chronic rhinosinusitis with nasal polyps JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00732-2019 SP - 1900732 AU - Yang Peng AU - Xiao-xue Zi AU - Teng-fei Teng 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 - 2019/01/01 UR - http://erj.ersjournals.com/content/early/2019/08/14/13993003.00732-2019.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 non-polyp 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, and gene sets that enriched in functional pathways.Measurement and main 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 differentially expressed genes (DEGs) between CRSwNP-NP and CS-IT, and between CRSwNP-NP and CRSwNP-IT tissues, respectively. Atopy status didn't have a major impact on the gene expression in various tissues. Gene Ontology analysis on these DEGs implicated extracellular matrix 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-defenses (including cilia dysfunction and immune dysregulation), inflammation and abnormal metabolism of extracellular matrix are implicated in CRSwNP. Functional validation of these gene expression patterns will open opportunities for CRSwNP therapeutic interventions such as biologics and immunomodulators.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Peng has nothing to disclose.Conflict of interest: Dr. Zi has nothing to disclose.Conflict of interest: Dr. Teng has nothing to disclose.Conflict of interest: Dr. Lee has nothing to disclose.Conflict of interest: Dr. Lum has nothing to disclose.Conflict of interest: Dr. Tang has nothing to disclose.Conflict of interest: Dr. Tan has nothing to disclose.Conflict of interest: Dr. Qiu has nothing to disclose.Conflict of interest: Dr. Ye has nothing to disclose.Conflict of interest: Dr. Shi reports grants from The Key Research Development Program of Shandong Province, outside the submitted work.Conflict of interest: Dr. Guan reports grants from Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme, during the conduct of the study.Conflict of interest: Dr. Andiappan reports grants from National Medical Research Council of Singapore, during the conduct of the study.Conflict of interest: Dr. Wang reports grants from National Medical Research Council of Singapore, outside the submitted work. ER -