Increased expression of hPGDS‑PGD2 in patients with eosinophilic chronic rhinosinusitis with nasal polyps

The existing studies on the hPGDS–PGD2 pathway in chronic rhinosinusitis with nasal polyps (CRSwNP) mostly focus on the tissue-level expression characteristics of single molecules and lack systematic correlation verification between peripheral circulating indicators and local lesion indicators, and few studies have specifically explored the differential diagnostic efficacy and early clinical application potential of serum PGD2 for eosinophilic CRSwNP (eCRSwNP). On the basis of filling the above research gaps, this study aimed to systematically investigate the expression characteristics of hPGDS-PGD2 signal pathway in eCRSwNP patients, and further evaluate the accurate clinical value of serum PGD2 as a non-invasive biomarker for early diagnosis and phenotypic identification of eCRSwNP. This prospective study enrolled patients diagnosed with CRSwNP or chronic rhinosinusitis without nasal polyps (CRSsNP) who underwent endoscopic sinus surgery (ESS) at our hospital between October 2022 and April 2024. Patients undergoing surgery for simple nasal septum deviation or traumatic nasal bone fracture during the same period served as the control group. Serum PGD2 levels were measured by enzyme‑linked immunosorbent assay (ELISA). Protein expression of hPGDS in nasal tissues was detected by Western blot and immunohistochemistry, and mRNA expression of hPGDS was determined by real‑time quantitative polymerase chain reaction (RT‑qPCR). Statistical analyses were performed using appropriate statistical software. (1) Peripheral blood eosinophil (EOS) count, EOS%, serum total IgE, and serum PGD2 levels were significantly higher in the eCRSwNP group than in the non‑eCRSwNP, CRSsNP, and control groups ( P < 0.05). (2) The total CT score and E/M ratio of paranasal sinus were both significantly higher in the eCRSwNP group than in the non‑eCRSwNP and CRSsNP groups. (3) Immunohistochemical staining intensity, Western blot gray value, and mRNA expression of hPGDS in nasal polyp tissues were significantly higher in the eCRSwNP group than in the non‑eCRSwNP and CRSsNP groups ( P < 0.05). (4) Serum PGD2 was positively correlated with hPGDS mRNA expression in nasal polyp tissues ( r = 0.398, P < 0.05) and showed statistically significant positive correlations with peripheral blood EOS count, serum total IgE, and E/M ratio ( P < 0.05). (5) Serum PGD2 exhibited diagnostic value for eCRSwNP (AUC = 0.775, P < 0.05), with accuracy comparable to peripheral blood EOS count, EOS%, serum total IgE, total CT score, and E/M ratio. The pathway-specific molecular axis of hPGDS-PGD2 is confirmed to be a key pathogenic mechanism of eCRSwNP. Clinically, serum PGD2, as a novel non-invasive peripheral biomarker, avoids the limitations of traditional invasive tissue detection and cumbersome imaging evaluation, and can be used for early screening, phenotypic differentiation and auxiliary diagnosis of eCRSwNP, solving the clinical pain point of difficult early precise identification of eCRSwNP. Meanwhile, the confirmed aberrant activation of the hPGDS-PGD2 pathway may offer a promising therapeutic strategy to overcome the refractory and recurrent nature of eCRSwNP.