转录组
鼻息肉
基因表达
生物
基因
免疫学
基因表达谱
发病机制
候选基因
血管生成
遗传学
作者
Yang Peng,Xiao-Xue Zi,Tengfei Tian,Bernett Lee,Josephine Lum,See Aik Tang,Kai Tan,Qianhui Qiu,Jing Yong Ye,Li Shi,Wei-jie Guan,Anand Kumar Andiappan,Dayong Wang
出处
期刊:The European respiratory journal
[European Respiratory Society]
日期:2019-01-01
卷期号:54 (5): 1900732-1900732
被引量:32
标识
DOI:10.1183/13993003.00732-2019
摘要
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.
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