Comprehensive proteomic analysis reveals SPRR3 as an early predictive biomarker for postoperative recurrence in pediatric chronic rhinosinusitis with nasal polyps

Background Pediatric chronic rhinosinusitis with nasal polyps (CRSwNP) exhibits a high rate of postoperative recurrence, yet effective molecular predictors remain lacking. This study aims to explore recurrence-associated proteins and evaluate their predictive value. Methods Proteomic analysis was performed on nasal mucosa from a discovery cohort, with >1 year of follow-up to identify differentially expressed proteins (DEPs) associated with postoperative recurrence. Candidate proteins were validated in an independent cohort using western blotting, immunofluorescence, qRT-PCR, and serum ELISA. Results In the discovery cohort, 6 pediatric patients suffering postoperative recurrence were classified as rCRSwNP, and 10 as non-rCRSwNP. Proteomic analysis revealed distinct expression patterns among control, non-rCRSwNP, and rCRSwNP groups. Four candidate proteins (CERS4, PLEKHA6, RAB29, SPRR3) were identified by intersecting the top 50 DEPs. SPRR3 and RAB29 were significantly upregulated in rCRSwNP, primarily localized to the nasal epithelium, as confirmed by western blotting and immunofluorescence. qRT-PCR further validated their increase in the recurrence group. Notably, paired tissue samples showed increased SPRR3 expression at revision surgery compared to baseline, and ELISA revealed higher serum SPRR3 levels in recurrent cases, correlating with recurrence risk. ROC and Kaplan–Meier analyses demonstrated potential predictive value for serum SPRR3. Conclusion Our study identified a recurrence-associated proteomic signature in pediatric CRSwNP, marked by selective epithelial upregulation of SPRR3. Elevated serum SPRR3 was strongly linked to postoperative recurrence risk, supporting its utility as a predictive biomarker for identifying children at higher risk of relapse.