Discrepant expression and prognostic role of epidermal growth factor receptor and icotinib radiosensitization for nasopharyngeal carcinoma

Abstract

Background: Epidermal growth factor receptor (EGFR) expression was observed in many tumors. Icotinib (IH), an EGFR tyrosine kinase inhibitor, could enhance the radiosensitivity, but few studies have focused on nasopharyngeal carcinoma (NPC). Materials and Methods : One hundred fifteen NPC lesions and 30 nasopharyngitis lesions were enrolled for EGFR expression evaluation with immunohistochemical staining. The correlation of EGFR expression and clinical parameters was analyzed. Survival analysis was calculated using univariate and multivariate analysis. A radioresistant NPC cell line, CNE-2R, was established with a gradient irradiation schedule of 60 Gy from CNE-2. Cell viability of CNE-2/2R was detected using microculture tetrazolium assay and colony-forming assay. The IH radiosensitization effect and EGFR expression were also evaluated in CNE-2/2R. Results: High EGFR expression was more frequently detected in NPC lesions (73/115) than chronic nasopharyngitis lesions (5/30, p =0.000). EGFR expression was correlated with tumor stage ( p =0.000) and tumor-node-metastasis (TNM) stage ( p =0.006). EGFR expression was an independent prognostic factor of disease-free survival ( p =0.047) and overall survival ( p =0.016). The optical density value of CNE-2R was higher than CNE-2 on days 1, 2, 4, and 6 after radiation of 4 Gy ( p <0.005). CNE-2 colony numbers clearly decreased compared with CNE-2R ( p <0.05), and IH enhanced the radiosensitizing effect of CNE-2R with an apparently lower survival fraction (1.414 times, p <0.05). Higher EGFR expression was observed in CNE-2R cells and decreased accordingly when exposed to IH. Conclusion: High EGFR expression was more frequently detected as a poor prognostic factor in NPC patients. Higher radioresistance and EGFR expression were observed in CNE-2R, and IH could reduce it. These results provided a new theoretical basis for clinical application of icotinib radiosensitization in NPC radiotherapy.