Serum proteomics identify CSF1R as a novel biomarker for postoperative recurrence in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) presents a high rate of postoperative recurrence, but its recurrent mechanisms are not fully clarified. In this study, we aim to explore biomarkers associated with the recurrence of CRSwNP and shed light on the underlying recurrent mechanisms using serum proteomics. A prospective cohort of CRSwNP patients was conducted, and serum samples were subjected to proteomic profiling. Participants were followed up for 2 years and divided into non-Recurrence and Recurrence groups and differentially expressed proteins (DEPs) were compared. The top 3 DEPs were validated in the serum and tissue samples in a validation cohort, and their predictive values for recurrence and their associations with macrophages were evaluated. In vitro, circulating macrophages were utilized to explore the influence of candidate proteins on macrophage polarization in underlying recurrent mechanisms of CRSwNP. Sixteen CRSwNP patients completed the follow-up schedule, including 10 patients in the non-Recurrence group and 6 patients in the Recurrence group. Serum proteomics revealed a distinctive protein expression profile between the 2 groups. A validation cohort comprising 51 non-recurrent and 24 recurrent CRSwNP patients was recruited. Enzyme-linked immunosorbent assay (ELISA) results revealed that circulating levels of CSF1R and CDC42 were significantly higher, and DHRS9 levels were lower in the Recurrence group in comparison with the non-Recurrence group. In addition, tissue CSF1R and CDC42 were identified to be enhanced in the Recurrence group compared to the non-Recurrence group. Receiver-operated characteristic (ROC) curves and Kaplan-Meier survival analysis suggest that both serum and tissue CSF1R were associated with the risk of postoperative recurrence. Tissue immunofluorescence (IF) revealed that CSF1R was enhanced in the tissues of patients with recurrence, especially in the mesenchymal region. Multiplex IF highlighted that CSF1R was significantly co-expressed with M2 macrophage markers. In vitro experiments confirmed that CSF1R overexpression promoted macrophage M2 polarization and cytokine production. Serum proteomic signatures may affect postoperative recurrence in CRSwNP patients. CSF1R is a potential biomarker for predicting CRSwNP recurrence. Mechanistically, the recurrence of CRSwNP appears to involve the CSF1R-driven M2 polarization process.