High VRK2 expression level predicts unfavorable survival outcomes in nasopharyngeal carcinoma.

[[abstract]]Background Epstein–Barr virus (EBV)–associated nasopharyngeal carcinoma (NPC) is an endemic epithelial malignancy in East and Southeast Asia, yet reliable molecular markers for risk stratification remain limited. Vaccinia-related kinase 2 (VRK2), a serine/threonine kinase implicated in cell proliferation, stress responses, and inflammatory signaling, has not been comprehensively evaluated in NPC. Methods In this retrospective study, we assessed the prognostic impact of VRK2 expression in 124 patients with histologically confirmed NPC. VRK2 protein levels were determined by immunohistochemical staining and correlated with clinicopathological parameters and survival outcomes. Results High VRK2 expression was significantly associated with advanced pathological stage (p = 0.006). Patients with high VRK2 levels had markedly poorer disease-specific survival (DSS), distant metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) on univariate analysis (all p < 0.001). In multivariate Cox regression models, elevated VRK2 expression remained an independent predictor of adverse outcomes, with hazard ratios of 2.904 (95% CI: 1.678–5.026) for DSS, 3.566 (95% CI: 1.874–6.784) for DMeFS, and 2.885 (95% CI: 1.411–5.898) for LRFS (all p < 0.001). Conclusions These findings suggest that VRK2 may actively contribute to the aggressive phenotype and enhanced progression of Epstein–Barr virus (EBV)-associated NPC by modulating cellular signaling pathways. The overexpression of VRK2 may reflect underlying molecular alterations associated with metastasis and treatment resistance. Therefore, VRK2 expression may serve not only as a clinically relevant prognostic biomarker but also as a potential molecular target to improve patient stratification and guide individualized therapeutic interventions in NPC.