Association of Increased Nasal Fluids-Serum Concordance of Protein Profile with Prognosis in Nasal Polyps

Yilin Hou,1– 5 Lin Sun,2– 5 Changhui Chen,2– 5 Mengqi Su,6 Shimin Lai,2– 5 Yan Yan,2– 5,7 Jieying Yan,2– 5 Rongjian Zhan,2– 5 Yongjin Su,1 Weiqiang Yang,1 Yi Wei,2– 5 Weiping Wen,2– 5,7 Hongyi Hu1 1Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, People’s Republic of China; 2Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 5Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, People’s Republic of China; 6Department of Cardiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 7Department of Otorhinolaryngology, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Hongyi Hu, Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong, 518036, People’s Republic of China, Email [email protected]: Predicting postoperative nasal polyp recurrence (PR) remains challenging because existing approaches rely on single clinical samples and thus fail to capture the complex, multi-compartment biology of the disease. This study aims to determine whether nasal fluid (NF) and serum protein concordance, reflecting the degree of coupling between local nasal and systemic inflammation, provides a more integrated prognostic signature for PR.Patients and Methods: Using the proximity extension assay (PEA), we quantified 92 proteins in NF and serum from 54 nasal polyps (NPs) patients (including 18 PR and 36 non-PR). In this prospective study, with PR assessed after a minimum follow-up of 6 months, NF-serum protein concordance was comprehensively assessed for associations with disease features and PR. Kaplan-Meier analysis and univariate Cox regression identified PR-predictive biomarkers, validated via bulk RNA-seq, single-cell RNA-seq (scRNAseq), immunofluorescence, and public database analysis.Results: Proteomic analysis of NF and serum revealed distinct protein profiles between PR and non-PR groups. Elevated NF-serum concordance was observed in current smokers and asthmatics, and positively correlated with eosinophil counts (r=0.26), pre-surgery Lund-Mackay (LM) scores (r=0.34), nasal VAS (r=0.26) and SNOT-22 scores (r=0.46) (Pearson’s test, all P< 0.05). Survival analysis demonstrated that higher NF-serum concordance predicted increased PR risk (HR=7.9, 95% CI=2.4– 25.6, P< 0.001). Univariate Cox regression identified leukemia inhibitory factor receptor (LIFR) as a novel PR biomarker (HR=2.1, 95% CI=1– 4.2, P< 0.05). Bulk RNA-seq confirmed LIFR upregulation in PR (P< 0.05), while scRNA-seq localized predominant LIFR expression to CRSwNP endothelial cells. Immunofluorescence verified LIFR-CD31 colocalization with stronger LIFR signals in PR (P< 0.05). Transcriptional (Twist1/NR2F2) and post-transcriptional (miRNA-mediated) regulatory mechanisms were implicated in LIFR-driven pathogenesis.Conclusion: Our study first investigated NF-serum proteomic concordance as a predictor of PR and demonstrated the potential of integrated multi-compartment analysis for predicting recurrence. Keywords: chronic rhinosinusitis with nasal polyps, nasal fluids, proteomics, polyps recurrence, bioinformatic analysis