COX-2 Expression and Mesenchymal-transition Status on Circulating Tumor Cells Predict Worse Survival in Patients with Nasopharyngeal Carcinoma: A Prospective Analysis

Abstract

The prognostic significance of circulating tumor cells (CTCs) in head and neck cancer is still under active investigation. It remains unclear whether just CTC count alone is sufficient to predict outcomes or whether the functional status of the CTCs is also needed. We investigated the clinical significance of determining epithelial-to-mesenchymal transition status and geno-/pheno-typic biomarkers of aggressiveness of CTCs in predicting outcomes in nasopharyngeal carcinoma (NPC). The prospective study enrolled 131 patients with NPC. CTCs were isolated at baseline and at the end of concurrent chemoradiotherapy using the CanPatrol system. Subsequently, the epithelial-mesenchymal transition (EMT) biomarkers and cyclooxygenase-2 (COX-2) expression status of the CTCs were identified by RNA-in situ hybridization (ISH) method. COX-2 expression was found in 87/131 (66.4%) patients at baseline and 53/115 (46.1%) patients post-treatment. Independent of initial COX-2 expression status, the patients with post-treatment COX-2 expression on CTCs had significantly poorer treatment response (P=0.011), and higher risk of tumor relapse (P=0.026) and metastasis (P=0.007). Similarly, post-treatment mesenchymal transition was also associated with higher risk of tumor relapse and metastasis. In multivariate analysis, post-treatment COX-2 expression on CTCs remained an independent prognostic indicator of poorer overall survival (HR 2.41, 95% CI 1.12-5.19; P=0.024). Post-treatment COX-2 expression and mesenchymal transition in CTCs was the strongest prognostic indicator of overall survival on multivariate analysis (HR 2.73, 95% CI 1.28-5.83; P=0.009). Post-treatment COX-2 expression on CTCs, especially on the mesenchymal subtype, is a novel and promising prognostic indicator for NPC patients treated with chemoradiation therapy. Future studies are needed to validate our findings and further clarify the value of integrating the indicators with current clinical strategies in improving survival of NPC patients.