Roundabout Guidance Receptor 1 Is an Emerging Prognostic Biomarker for Nasopharyngeal Carcinoma

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharynx with high morbidity and mortality in Southeast Asia and south of China. Roundabout guidance receptor 1 (ROBO1) can regulate axonogenesis (axon-like protrusion), which may play an important role in migration. However, the roles of ROBO1 in NPC have not been clarified. Methods: A comparative analysis employing the NPC transcriptome (GSE12452) and the axonogenesis-related genes (GO: 0050772) was performed. In total, 124 tissue blocks from patients primarily diagnosed as NPC (1993-2002) were examined using immunohistochemical staining. The connections between clinicopathological variables and protein immunoexpression were analyzed by Pearson’s chi-square test. The Kaplan–Meier method with a log-rank test was employed to plot survival curves. Multivariate analysis was performed using the Cox proportional hazards model to identify independent prognostic biomarker. Results: According to transcriptome analysis, we found that ROBO1 is significantly highly expressed in NPC tissues compared with normal tissues. The immunohistochemistry (IHC) staining showed that high expression of ROBO1 was significantly related to primary tumor (T1T2 and T3T4) ( P = .024), nodal metastasis status (N0N1 and N2N3) ( P = .030), stage (I-II and III-IV) ( P = .019), and histological grade (keratinizing, non-keratinizing, and undifferentiated) ( P = .065). Importantly, NPC patients with high ROBO1 expression had poorer disease-specific survival (DSS) ( P = .0001), distal metastasis-free survival (DMeFS) ( P < .0001), and local recurrence-free survival (LRFS) ( P = .0001) compared with NPC patients with low ROBO1 expression through the uni-/multivariate and the Kaplan–Meier survival analyses. Conclusion: Our report indicates that ROBO1 might be a potential prognostic biomarker for NPC.