Regenerating gene IA predicts radiosensitivity and survival in nasopharyngeal carcinoma.

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. Radiotherapy is the main treatment option. However, radiotherapy does not benefit all patients because there is no known precise biomarker that can be used for screening radioresistant patients. Genetic predisposition is closely related to tumor development, therapeutic response, and prognosis. The relationship between regenerating gene IA (REGIA) and NPC is unclear. This study aimed to retrospectively analyze the association between REGIA expression and metastasis, radiosensitivity, and survival in patients with NPC as well as assess the effect of radiation on REGIA expression in vitro. Immunohistochemical staining was used to detect REGIA. The relationship between REGIA expression in radioresistant NPC and the prognosis of CNE1 NPC cells were analyzed using quantitative real-time polymerase chain reaction and Western blotting. We found that increased doses of radiation in CNE1 cells significantly decreased REGIA expression (P<0.05). The overall rate of REGIA-positive expression was 47.15% in NPC tissues and 45.00% and 61.02% in radiosensitive and radioresistant cases, respectively, showing significant differences (P<0.05). A REGIA-positive protein expression rate had a negative correlation with radiosensitivity in NPC (r= -0.109, P=0.047). Both REGIA-positive and REGIA-negative expression strongly predicted the overall survival rate and progression-free survival of NPC patients (P<0.01). A multivariate analysis indicated that REGIA was an inverse prognostic factor in NPC patients (REGIA-positive expression hazard ratio (HR)=2.139, 95% confidence interval (CI)=1.56-2.94, P<0.001 and REGIA-negative expression HR=1.958, 95% CI=1.42-2.69, P<0.001). In conclusion: Radiation can affect REGIA expression. The REGIA expression level correlated with radioresistance and a poor prognosis. In addition, REGIA expression might act as a potential therapeutic target and prognostic predictor in NPC patients.