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伴鼻息肉慢性鼻-鼻窦炎的转录组特征及功能网络分析

Transcriptomic Signatures and Functional Network Analysis of Chronic Rhinosinusitis With Nasal Polyps.

作者信息

Hao Yun, Zhao Yan, Wang Ping, Du Kun, Li Ying, Yang Zhen, Wang Xiangdong, Zhang Luo

机构信息

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

出版信息

Front Genet. 2021 Feb 2;12:609754. doi: 10.3389/fgene.2021.609754. eCollection 2021.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease with limited treatment options of corticosteroids, sinus surgery, or both. CRSwNP is frequently associated with allergic rhinitis and asthma, but the molecular mechanisms underlying CRSwNP inflammation are not completely understood. We obtained four gene expression profiles (GSE136825, GSE36830, GSE23552, and GSE72713) from four Gene Expression Omnibus (GEO), which collectively included 65 nasal polyp samples from CRSwNP patients and 54 nasal mucosal samples from healthy controls. Using an integrated analysis approach, we identified 76 co-differentially expressed genes (co-DEGs, including 45 upregulated and 31 downregulated) in CRSwNP patients compared with the healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified the terms including immune effector process, leukocyte migration, regulation of the inflammatory response, infection, and cytokine-cytokine receptor interaction. protein-protein interaction (PPI) network analysis and real-time quantitative PCR (RT-qPCR) showed that 7 genes might be crucial in CRSwNP pathogenesis. Repurposing drug candidates (Alfadolone, Hydralazine, SC-560, Iopamidol, Iloprost, etc) for CRSwNP treatment were identified from the Connectivity Map (CMap) database. Our results suggest multiple molecular mechanisms, diagnostic biomarkers, potential therapeutic targets, and new repurposing drug candidates for CRSwNP treatment.

摘要

伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)是一种慢性鼻窦炎性疾病,治疗选择有限,包括使用皮质类固醇、鼻窦手术或两者并用。CRSwNP常与过敏性鼻炎和哮喘相关,但CRSwNP炎症的分子机制尚未完全明确。我们从四个基因表达综合数据库(GEO)中获取了四个基因表达谱(GSE136825、GSE36830、GSE23552和GSE72713),这些数据总共包括65例CRSwNP患者的鼻息肉样本和54例健康对照的鼻黏膜样本。采用综合分析方法,我们鉴定出与健康对照相比,CRSwNP患者中有76个共差异表达基因(共DEG,包括45个上调基因和31个下调基因)。基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析确定了包括免疫效应过程、白细胞迁移、炎症反应调节、感染以及细胞因子-细胞因子受体相互作用等术语。蛋白质-蛋白质相互作用(PPI)网络分析和实时定量PCR(RT-qPCR)表明,7个基因可能在CRSwNP发病机制中起关键作用。从连接图谱(CMap)数据库中确定了用于CRSwNP治疗的药物候选物(阿法多龙、肼屈嗪、SC-560、碘帕醇、伊洛前列素等)。我们的研究结果提示了CRSwNP治疗的多种分子机制、诊断生物标志物、潜在治疗靶点以及新的药物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32ce/7884819/b98afd07d1d7/fgene-12-609754-g0001.jpg

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