Diagnostic and prognostic value of EphB2 in nasopharyngeal carcinoma

• We improve the sensitivity and specificity of early screening for nasopharyngeal carcinoma. • We offer a theoretical basis for the early prediction of the prognosis for nasopharyngeal carcinoma. • We first report the association of EphB2 with EBV infection in NPC. • This work establishes a foundational framework for future clinical trials exploring EPHB2-targeted agents in combination with existing immunotherapies, potentially leading to improved outcomes for NPC patients. Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC. Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, P < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, P < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, P < 0.001), with 78.6 % sensitivity and 97.5 % specificity. Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.