Identification Of Aurora-A And C-Met As Recurrence Predictor And Therapeutic Target For Nasopharyngeal Carcinoma.

e23171 Background: Among patients with locally advanced nasopharyngeal carcinoma (NPC) in endemic Southern China area, 30.0%-50.0% subset would develop recurrence or metastasis within 5 years after treatment. Identification recurrence related molecules might allow for timely identification of recurrence and target therapy for NPC. Methods: To identify candidate recurrence related molecules, we profiled global gene expression in NPC with a patient survival dataset. On the basis of The Cancer Genome Atlas (TCGA) analysis, we further selected the molecules with high risk for NPC recurrence. Moreover, xenograft animal model and 130 locally advanced NPC patients samples were used to validate the potential to target the selected molecules to prevent NPC recurrence. Results: Based on TCGA analysis and our previously constructed database, we selected 30 molecules that might be contributed to NPC recurrence: Cyclin D1, 14-3-3σ, Aurora-A, CENP-H, Stathmin, P21, CDC2, P27, ERK, p-ERK, Ki-67, E-Cadherin, β-Catenin, N-Cadherin, Snail, Twist, C-Met, nm23-H1, HIF-1α, COX2, MMP-2, MMP-9, TIMP-2, Bax, Bcl-2, Survivin, AKT 1, Beclin 1, EZH2, and LMP 1. Univariate and multivariate analyses confirmed that Aurora-A, MMP-9 and C-Met were independent prognostic biomarker to predict NPC recurrence (with all P < 0.05). For CNE-1 and CNE-2 NPC cells, VX-680, an Aurora-A specific inhibitor, and SU11274, a specific C-Met inhibitor, combined treatment significantly increased NPC cell sensitivity to radiation. Moreover, the similar results were also observed in NPC nude mice xenograft mode. We had construct the Aurora-A/C-met high expressed and Aurora-A/C-met low expressed PDX SCID mice, the combined therapeutic effect to radiation are ongoing testing. Conclusions: Based on this nonbiased method, we identified Aurora-A, C-Met and MMP-9 were the potential prognostic biomarker to predict NPC recurrence. Target Aurora-a and C-met with their specific inhibitor sensitized the NPC cell and tumor xenograft mice model to radiation, suggesting a promising way to upregulate radiosensitivity and abate radioresistant residue induced recurrence for nasopharyngeal carcinoma.