International Rhinologic Society Rhinology 0300-0729 2026 05 20 CTSS as a novel biomarker for tissue remodeling in CRSwNP: insights from multi-omics research EN C. LiDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Y. HuangDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China J. YanDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Y. YanOtorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Department of Otolaryngology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Y. GuoDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China K. LiDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Y. WenDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China J. LiDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Y. WeiDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China W. WenDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Department of Otolaryngology, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen Z. XuDepartment of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China Journal Article 3458 10.4193/Rhin25.504 BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory, relapsing upper airway inflammatory disorder cha-racterized by prominent tissue remodeling. Current therapeutic options remain suboptimal. We aimed to identify novel potential targets and biomarkers using integrative multi-omics. METHODOLOGY: We performed Mendelian randomization (MR) analyses integrating blood expression quantitative trait loci (eQTL) from eQTLGen and plasma protein quantitative trait loci (pQTL) from deCODE with nasal polyps (NP) genome-wide association study data from 8,496 NP patients and 371,520 controls. Significant targets underwent validation via bulk/single-cell RNA sequen-cing, immunohistochemistry, and immunofluorescence. RESULTS: MR analyses identified 6 targets causally linked to NP risk in both eQTL and pQTL analyses. Therein, cathepsin S (CTSS) increased the risk of NP, exclusively demonstrating colocalization with NP and exhibiting significant upregulation in NP tissue. Single-cell data showed CTSS mainly express in monocyte/macrophages, and CTSS-high subsets enriched in CRSwNP vs. Control. Immunohistochemistry and immunofluorescence further confirmed high CTSS expression in NP. Moreover, CTSS expression cor-related with tissue remodeling pathways and associated with CRSwNP clinical severity. CONCLUSIONS: CTSS may contribute to the pathogenesis of CRSwNP by modulating tissue remodeling. CTSS is a noval biomarker for CRSwNP.