关键词: AZGP1 EGF bioinformatics analysis chronic rhinosinusitis with nasal polyps differentially expressed genes

来  源:   DOI:10.2147/JIR.S428238   PDF(Pubmed)

Abstract:
UNASSIGNED: The mechanisms underlying the chronic rhinosinusitis with nasal polyps (CRSwNP) remained unclear. This study aimed to identify differentially expressed genes (DEGs) in nasal polyps from CRSwNP patients compared to healthy controls and explore key genes and pathways associated with CRSwNP pathophysiology and prognosis.
UNASSIGNED: Three datasets were obtained from the Gene Expression Omnibus database and the intersecting DEGs were identified in CRSwNP patients. Gene Ontology (GO) and protein-protein interaction (PPI) network analysis were applied to investigate the function of DEGs. Nasal specimens from 90 CRSwNP and 45 controls were further collected and qRT-PCR was applied to verify the mRNA expression of hub genes, and moreover, their association with tissue eosinophilia and clinical characteristics in CRSwNP were analyzed.
UNASSIGNED: Sixty-eight co-DEGs including 8 upregulated and 60 downregulated genes were identified and GO analyses identified the terms including positive regulation of ERK1 and ERK2 cascade, transforming growth factor beta receptor signaling pathway. PPI networks identified hub genes including EGF, ERBB4, AZGP1, CRISP3 and PIP which were validated to be significantly down-regulated in CRSwNP and showed well diagnostic prediction quality. In addition, lower mRNA expressions level of EGF and AZGP1 in eosinophilic CRSwNP compared with non-eosinophilic CRSwNP were found. Aberrant low expressions of EGF and AZGP1 protein in CRSwNP were identified, and there was good consistency between their mRNA expression level and protein relative expression level. Furthermore, the expressions of EGF and AZGP1 mRNA were significantly correlated with clinical severity parameters.
UNASSIGNED: Integrated analysis revealed 68 co-DEGs between nasal polyps and controls and identified hub genes, of which EGF and AZGP1 expression was significantly downregulated in eosinophilic CRSwNP and correlated with disease severity. Downregulation of EGF and AZGP1 may contribute to epithelial barrier dysfunction and type 2 inflammation in CRSwNP, suggesting them as potential diagnostic biomarkers and therapeutic targets.
摘要:
慢性鼻窦炎伴鼻息肉(CRSwNP)的潜在机制仍不清楚。本研究旨在鉴定CRSwNP患者鼻息肉与健康对照的差异表达基因(DEGs),并探索与CRSwNP病理生理和预后相关的关键基因和通路。
从基因表达综合数据库获得三个数据集,并且在CRSwNP患者中鉴定出相交的DEGs。应用基因本体论(GO)和蛋白质-蛋白质相互作用(PPI)网络分析来研究DEGs的功能。进一步收集来自90个CRSwNP和45个对照的鼻腔标本,并应用qRT-PCR验证hub基因的mRNA表达。而且,分析其与CRSwNP中组织嗜酸性粒细胞增多和临床特征的关系.
鉴定出包括8个上调和60个下调基因的68个co-DEG,GO分析鉴定出包括ERK1和ERK2级联的正调节的术语,转化生长因子β受体信号通路。PPI网络确定了集线器基因,包括EGF,ERBB4、AZGP1、CRISP3和PIP被证实在CRSwNP中显著下调,并显示良好的诊断预测质量。此外,与非嗜酸性CRSwNP相比,嗜酸性CRSwNP中EGF和AZGP1的mRNA表达水平较低。鉴定了EGF和AZGP1蛋白在CRSwNP中的异常低表达,mRNA表达水平与蛋白相对表达水平具有较好的一致性。此外,EGF和AZGP1mRNA的表达与临床严重程度参数显着相关。
综合分析显示,鼻息肉与对照之间存在68个co-DEG,并确定了hub基因,其中EGF和AZGP1表达在嗜酸性粒细胞CRSwNP中显著下调,并与疾病严重程度相关。EGF和AZGP1的下调可能导致CRSwNP的上皮屏障功能障碍和2型炎症。提示它们是潜在的诊断生物标志物和治疗靶点。
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