{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:17:35Z","timestamp":1753870655703,"version":"3.41.2"},"reference-count":58,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["World j. otorhinolaryngol.-head neck surg."],"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic rhinosinusitis (CRS) and nasal polyps (NP) are chronic inflammatory conditions with unsatisfactory treatment outcomes due to frequent recurrence of refractory disease. Identifying new therapeutic targets is essential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a proteome\u2010wide Mendelian randomization (MR) analysis by integrating genome\u2010wide association study genomic data of CRS\/NP with cis\u2010proteomic quantitative trait locus data to identify plasma proteins associated with CRS\/NP risk. We validated the main findings using the Steiger test, Bayesian colocalisation, summary\u2010data\u2010based MR, and proteome\u2010wide association studies. Single\u2010cell expression analysis, enrichment analysis, protein\u2013protein interaction networks, and drug availability assessments were performed to elucidate the functional pathways of the proteins and explore their potential as therapeutic targets for CRS\/NP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified nine proteins associated with the risk of NP and four proteins associated with the risk of CRS through proteome\u2010wide MR analysis. Among these, three proteins (IL2RB, IL7R, and POR) associated with NP demonstrated the highest level of evidence and were prioritized. The protein\u2010coding genes were primarily expressed in early secretory cells, tuft cells, ionocyte cells, basal cells, and secretory cells. These genes play significant roles in regulating the adaptive immune response and cytokine\u2013cytokine receptor interaction. Four proteins (IL2RB, IL7R, POR, and TNFSF11) interacted with known drug targets for NP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study prioritizes IL2RB and IL7R as key mediators of CRS\/NP pathogenesis via immune dysregulation. Their interactions with existing biologics underscore translational potential, offering mechanistic insights and actionable targets for biotherapy development.<\/jats:p><jats:p><jats:bold>Clinical trial number:<\/jats:bold> Not applicable.<\/jats:p><\/jats:sec>","DOI":"10.1002\/wjo2.70038","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T05:54:26Z","timestamp":1751435666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Analysis of Plasma Proteome and Genome Reveals Novel Drug Targets for Chronic Rhinosinusitis and Nasal Polyps"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-1873","authenticated-orcid":false,"given":"En","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck surgery Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery The Affiliated Zhuzhou Hospital Xiangya Medical College CSU Zhuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck surgery Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck surgery Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu\u2010Ping","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck surgery Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"3","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2012","volume":"23","author":"Fokkens W. 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