Abstract
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.
Abstract
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
Footnotes
This article has supplementary material available from erj.ersjournals.com
Author contributions: Conceived and designed the experiments: D.Y. Wang, A.K. Andiappan and W-J. Guan. Collection of samples: Y. Peng, X-X. Zi, T-F. Tian, L. Shi, J. Ye and Q-H. Qiu. Performed the experiments: Y. Peng, X-X. Zi, T-F. Tian and A.K. Andiappan. Data analysis: A.K. Andiappan, Y. Peng, X-X. Zi, T-F. Tian, W-J. Guan, B. Lee, J. Lum, S.A. Tang and K.S. Tan. Contributed reagents/materials/analysis tools: A.K. Andiappan and D.Y. Wang. Wrote the paper: W-J. Guan, A.K. Andiappan, K.S. Tan, Y. Peng, X-X. Zi, T-F. Tian. Critical review and approval: A.K. Andiappan, D.Y. Wang and W-J. Guan.
Conflict of interest: Y. Peng has nothing to disclose.
Conflict of interest: X-X. Zi has nothing to disclose.
Conflict of interest: T-F. Tian has nothing to disclose.
Conflict of interest: B. Lee has nothing to disclose.
Conflict of interest: J. Lum has nothing to disclose.
Conflict of interest: S.A. Tang has nothing to disclose.
Conflict of interest: K.S. Tan has nothing to disclose.
Conflict of interest: Q-H. Qiu has nothing to disclose.
Conflict of interest: J. Ye has nothing to disclose.
Conflict of interest: L. Shi reports grants from The Key Research Development Program of Shandong Province (2018CXGC1214), outside the submitted work.
Conflict of interest: W-J. Guan reports grants from Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017, during the conduct of the study.
Conflict of interest: A.K. Andiappan reports grants from National Medical Research Council of Singapore (OFYIRG17nov065), during the conduct of the study.
Conflict of interest: D.Y. Wang reports grants from National Medical Research Council of Singapore (NMRC/CIRG/1458/2016), outside the submitted work.
Support statement: Supported by National Medical Research Council of Singapore (NMRC/CIRG/1458/2016; D.Y. Wang), National Medical Research Council of Singapore (OFYIRG17nov065; A.K. Andiappan), The Key Research Development Program of Shandong Province (2018CXGC1214; L. Shi), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017 (201710010097; W-J. Guan), and the National Nature Science Foundation of China (81873690; Q-H. Qiu). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received April 11, 2019.
- Accepted August 8, 2019.
- Copyright ©ERS 2019
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