Soluble Guanylate Cyclase Dysfunction and Nitric Oxide Pathway in Chronic Rhinosinusitis With Nasal Polyps: Predictive Markers for Postoperative Recurrence

Background: Elevated nitric oxide (NO) levels have been linked to a heightened risk of recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the precise influence of NO on CRSwNP recurrence remains unclear. Objective: This study seeks to elucidate the relationship between NO levels and the risk of CRSwNP recurrence. Methods: A protein chip array analysis was conducted to identify differentially expressed inflammatory mediators in the nasal tissues between patients with CRSwNP and healthy controls (HC). Differentially expressed proteins were analyzed, and bioinformatics analysis was used to predict the potential functions and pathways of these proteins. Western blotting (WB) and immunohistochemistry were employed to validate the candidate proteins in 2 independent cohorts. Receiver-operating characteristic (ROC) curves were employed to assess the abilities of target proteins for predicting the postoperative recurrence of CRSwNP. Results: Twelve differentially expressed proteins were identified between the CRSwNP and HC groups. Notably, differentially expressed proteins exhibited high expression of the biological process term "positive regulation of nitric oxide-mediated signal transduction" (P < .05). WB and immunohistochemistry results demonstrated that guanylate cyclase 1 soluble subunit alpha 1 (GUCY1A1), GUCY1A2, nitric oxide synthase 1 adaptor protein, epidermal growth factor receptor, and insulin were found to be upregulated in the CRSwNP group compared to the HC group (P < .05). Moreover, elevated levels of GUCY1A2 and GUCY1A1 were observed to be associated with an increased risk of CRSwNP recurrence (P < .05), and ROC curve analysis confirmed their effectiveness as predictors for postoperative recurrence (P < .05). Conclusion: Our findings revealed that CRSwNP exhibited a distinct tissue protein profile, with soluble guanylate cyclase dysfunction and the nitric oxide pathway implicated in the underlying pathological mechanisms. The discovery-validation results suggested that GUCY1A1 and GUCY1A2 were promising predictors for postoperative recurrence in patients with CRSwNP.