Integrative Analysis of Plasma Proteome and Genome Reveals Novel Drug Targets for Chronic Rhinosinusitis and Nasal Polyps
Year: 2025
Type: article
Abstract: Background: 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. Methods: We conducted a proteome-wide Mendelian randomization (MR) analysis by integrating genome-wide association study genomic data of CRS/NP with cis-proteomic 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-data-based MR, and proteome-wide association studies. Single-cell expression analysis, enrichment analysis, protein-protein 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. Results: We identified nine proteins associated with the risk of NP and four proteins associated with the risk of CRS through proteome-wide MR analysis. Among these, three proteins (IL2RB, IL7R, and POR) associated with NP demonstrated the highest level of evidence and were prioritized. The protein-coding 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-cytokine receptor interaction. Four proteins (IL2RB, IL7R, POR, and TNFSF11) interacted with known drug targets for NP. Conclusions: Not applicable.
DOI: 10.1002/wjo2.70038
Authors: En Zhou, Shi Luo, Yu Xiao, Bin Liu, Xu‐Ping Xiao
Institutions: Hunan Normal University, Hunan Provincial People's Hospital
Language: English
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4411969554