{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:29:06Z","timestamp":1788834546719,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>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 (<jats:ext-link>GSE136825<\/jats:ext-link>, <jats:ext-link>GSE36830<\/jats:ext-link>, <jats:ext-link>GSE23552<\/jats:ext-link>, and <jats:ext-link>GSE72713<\/jats:ext-link>) 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, <jats:italic>Staphylococcus aureus<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fgene.2021.609754","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T20:31:09Z","timestamp":1612297869000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Transcriptomic Signatures and Functional Network Analysis of Chronic Rhinosinusitis With Nasal Polyps"],"prefix":"10.3389","volume":"12","author":[{"given":"Yun","family":"Hao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The gene ontology consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-4-2","article-title":"An automated method for finding molecular complexes in large protein interaction networks","volume":"4","author":"Bader","year":"2003","journal-title":"BMC Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"36709","DOI":"10.1074\/jbc.M111.291492","article-title":"Hck is a key regulator of gene expression in alternatively activated human monocytes","volume":"286","author":"Bhattacharjee","year":"2011","journal-title":"J. Biol. Chem"},{"key":"B4","doi-asserted-by":"publisher","first-page":"484.e471","DOI":"10.1016\/j.jaci.2009.05.017","article-title":"Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese","volume":"124","author":"Cao","year":"2009","journal-title":"J. Allergy. Clin. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/j.1398-9995.2010.02514.x","article-title":"Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics","volume":"66","author":"Cheong","year":"2011","journal-title":"Allergy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4261","DOI":"10.1038\/srep04261","article-title":"CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation","volume":"4","author":"Federzoni","year":"2014","journal-title":"Sci. Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/Rhino50E2","article-title":"European position paper on rhinosinusitis and nasal polyps 2012","volume":"23","author":"Fokkens","year":"2012","journal-title":"Rhinol. Suppl"},{"key":"B8","doi-asserted-by":"publisher","first-page":"D322","DOI":"10.1093\/nar\/gkj021","article-title":"The gene ontology (GO) PROJECT in 2006","volume":"34","author":"Gene Ontology","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nrg.2016.49","article-title":"Coming of age: ten years of next-generation sequencing technologies","volume":"17","author":"Goodwin","year":"2016","journal-title":"Nat. Rev. Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2680","DOI":"10.1172\/JCI97945","article-title":"Leukotriene biosynthetic enzymes as therapeutic targets","volume":"128","author":"Haeggstrom","year":"2018","journal-title":"J. Clin. Invest"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1111\/j.1398-9995.2011.02646.x","article-title":"Chronic rhinosinusitis in Europe\u2013an underestimated disease. A GA(2)LEN study","volume":"66","author":"Hastan","year":"2011","journal-title":"Allergy"},{"key":"B12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41392-018-0013-x","article-title":"Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer","volume":"3","author":"Hiraki","year":"2018","journal-title":"Signal Transduct. Target Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1002\/alr.21114","article-title":"Gene expression differences in nitric oxide and reactive oxygen species regulation point to an altered innate immune response in chronic rhinosinusitis","volume":"3","author":"Jardeleza","year":"2013","journal-title":"Int. Forum Allergy Rhinol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"226","DOI":"10.4168\/aair.2011.3.4.226","article-title":"Chronic rhinosinusitis: therapeutic efficacy of anti-inflammatory and antibiotic approaches","volume":"3","author":"Kariyawasam","year":"2011","journal-title":"Allergy Asthma Immunol. Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.4168\/aair.2017.9.4.299","article-title":"Emerging endotypes of chronic rhinosinusitis and its application to precision medicine","volume":"9","author":"Kim","year":"2017","journal-title":"Allergy Asthma Immunol. Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1165\/rcmb.2008-0169TR","article-title":"MUC1 mucin: a peacemaker in the lung","volume":"39","author":"Kim","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/ncponc1187","article-title":"Strategies for discovering novel cancer biomarkers through utilization of emerging technologies","volume":"5","author":"Kulasingam","year":"2008","journal-title":"Nat. Clin. Pract. Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1165\/rcmb.2011-0142OC","article-title":"Antiinflammatory role of MUC1 mucin during infection with nontypeable haemophilus influenzae","volume":"46","author":"Kyo","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"534","DOI":"10.4168\/aair.2015.7.6.534","article-title":"Mechanisms of glucocorticoid action in chronic rhinosinusitis","volume":"7","author":"Lee","year":"2015","journal-title":"Allergy Asthma Immunol. Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"L558","DOI":"10.1152\/ajplung.00225.2009","article-title":"Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro","volume":"298","author":"Li","year":"2010","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3855","DOI":"10.3892\/mmr.2019.10005","article-title":"Genomewide profiling of lncRNA and mRNA expression in CRSwNP","volume":"19","author":"Liu","year":"2019","journal-title":"Mol. Med. Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.jaci.2014.07.011","article-title":"Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps","volume":"135","author":"Milara","year":"2015","journal-title":"J. Allergy Clin. Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1002\/pmic.201400515","article-title":"FunRich: an open access standalone functional enrichment and interaction network analysis tool","volume":"15","author":"Pathan","year":"2015","journal-title":"Proteomics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1900732","DOI":"10.1183\/13993003.00732-2019","article-title":"Whole-transcriptome sequencing reveals heightened inflammation and defective host defence responses in chronic rhinosinusitis with nasal polyps","volume":"54","author":"Peng","year":"2019","journal-title":"Eur. Respir. J"},{"key":"B27","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1089\/jamp.2015.1210","article-title":"Btk inhibitor RN983 delivered by dry powder nose-only aerosol inhalation inhibits bronchoconstriction and pulmonary inflammation in the ovalbumin allergic mouse model of asthma","volume":"29","author":"Phillips","year":"2016","journal-title":"J. Aerosol Med. Pulm. Drug Deliv"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e11450","DOI":"10.1371\/journal.pone.0011450","article-title":"Gene transcription changes in asthmatic chronic rhinosinusitis with nasal polyps and comparison to those in atopic dermatitis","volume":"5","author":"Plager","year":"2010","journal-title":"PLoS ONE"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4477-4","article-title":"HK3 overexpression associated with epithelial-mesenchymal transition in colorectal cancer","volume":"19","author":"Pudova","year":"2018","journal-title":"BMC Genomics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1111\/j.1365-2222.2009.03229.x","article-title":"Gene-expression profiles in human nasal polyp tissues and identification of genetic susceptibility in aspirin-intolerant asthma","volume":"39","author":"Sekigawa","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/all.12577","article-title":"Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities","volume":"70","author":"Shi","year":"2015","journal-title":"Allergy"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.jaci.2015.10.009","article-title":"Chronic rhinosinusitis pathogenesis","volume":"136","author":"Stevens","year":"","journal-title":"J. Allergy Clin. Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1164\/rccm.201412-2278OC","article-title":"Cytokines in chronic rhinosinusitis. Role in eosinophilia and aspirin-exacerbated respiratory disease","volume":"192","author":"Stevens","year":"","journal-title":"Am. J. Respir. Crit. Care Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.jaip.2016.04.012","article-title":"Chronic rhinosinusitis with nasal polyps","volume":"4","author":"Stevens","year":"2016","journal-title":"J. Allergy Clin. Immunol. Pract"},{"key":"B37","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.imlet.2017.08.016","article-title":"The phagocyte respiratory burst: historical perspectives and recent advances","volume":"192","author":"Thomas","year":"2017","journal-title":"Immunol. Lett"},{"key":"B39","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/ctm2.6","article-title":"HK3 is correlated with immune infiltrates and predicts response to immunotherapy in non-small cell lung cancer","volume":"10","author":"Tuo","year":"2020","journal-title":"Clin. Transl. Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"26604","DOI":"10.1038\/srep26604","article-title":"Transcriptome analysis reveals distinct gene expression profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.jaci.2016.05.041","article-title":"Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania","volume":"138","author":"Wang","year":"2016","journal-title":"J. Allergy Clin. Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.cell.2016.05.076","article-title":"Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan","volume":"166","author":"Wolf","year":"2016","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.iac.2018.06.006","article-title":"Biomarkers in chronic rhinosinusitis with nasal polyps","volume":"38","author":"Workman","year":"2018","journal-title":"Immunol. Allergy Clin. North Am"},{"key":"B44","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B45","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.jaci.2008.07.008","article-title":"Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease","volume":"122","author":"Zhang","year":"2008","journal-title":"J. Allergy Clin. Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.7150\/jca.28077","article-title":"Salivary microbial dysbiosis is associated with systemic inflammatory markers and predicted oral metabolites in non-small cell lung cancer patients","volume":"10","author":"Zhang","year":"2019","journal-title":"J. Cancer"},{"key":"B47","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/alr.22530","article-title":"Expression of nicotinamide adenine dinucleotide phosphate oxidase in chronic rhinosinusitis with nasal polyps","volume":"10","author":"Zheng","year":"2020","journal-title":"Int. Forum Allergy Rhinol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"6140728","DOI":"10.1155\/2020\/6140728","article-title":"Identification of key modules, hub genes, and noncoding RNAs in chronic rhinosinusitis with nasal polyps by weighted gene coexpression network analysis","volume":"2020","author":"Zhou","year":"2020","journal-title":"Biomed. Res. Int"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.609754\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T20:31:11Z","timestamp":1612297871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.609754\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":48,"alternative-id":["10.3389\/fgene.2021.609754"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.609754","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]},"article-number":"609754"}}