Serum levels of EphA2 are elevated in knee osteoarthritis and associated with disease severity.

Background: This study investigated the clinical relevance of serum ephrin type-A receptor 2 (EphA2) in patients with knee osteoarthritis (OA) compared to healthy controls and its association with disease severity, inflammatory markers, oxidative stress, and cartilage metabolism. Methods: A total of 258 participants, including 138 patients with primary knee OA and 120 age- and sex-matched healthy controls, were recruited between January 2023 and December 2024. OA severity was assessed using the Kellgren-Lawrence grading system, and clinical symptoms were assessed using the WOMAC score. Statistical analyses included group comparisons, Pearson correlations with Benjamini-Hochberg FDR adjustment, ROC curves for diagnostic performance, and multivariate logistic regression to identify independent risk factors. Results: Among patients with knee OA, those with Kellgren-Lawrence (K-L) grade III-IV had significantly higher EphA2 levels than those with K-L grades I-II. Receiver operating characteristic (ROC) analysis determined an optimal EphA2 cut-off of 276.8 pg./mL, yielding 92% sensitivity, 72% specificity, and an AUC of 0.924. After false discovery rate (FDR) correction, EphA2 remained positively correlated with the WOMAC score ( Conclusion: These findings suggest that EphA2 is closely associated with cartilage degradation, inflammation, oxidative stress, and ferroptosis in knee OA and may serve as a promising biomarker for disease diagnosis and progression monitoring.