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

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.

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.

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.

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.