Predictive Value of ERCC1 mRNA Level and Pretreatment EBV-DNA Virus Load in Stage II Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy with Concurrent Cisplatin

Abstract

Background: The protein expression of ERCC1 in DNA repair genes was related to resistance platinum and predicting treatment outcomes in various malignant carcinoma ,the level of plasma Epstein-Barr virus（EBV）DNA concentrations is positively correlated with clinical stages of nasopharyngeal carcinoma(NPC), but the predictive value of ERCC1 mRNA and EBV-DNA level for stratified treatment with stage II NPC is unclear precisely. This study aimed to assess the predictive value of combined EBV-DNA and ERCC1 in stage II NPC patients treated with intensity-modulated radiotherapy (IMRT) with concurrent cisplatin and provide guidance for future stratified treatment.Methods: A total 78 stage II NPC patients who received IMRT and concurrent cisplatin-based chemotherapy had measurements of ERCC1 mRNA and pre-treatment EBV DNA levels by real-time PCR (RT-PCR) analysis were analyzed. Associations of ERCC1 mRNA and pre-treatment EBV DNA levels with clinical characteristics and survivals were evaluated.Results: Cut-off value of ERCC1 mRNA obtained from ROC curve was used and there were significant differences in progression-free survival (PFS) and overall survival (OS) between high expression group as compared to low expression group (P=0.021 and 0.030, respectively). Patients with pretreatment EBV-DNA<2000 copies/ml had significantly better PFS (P= 0.024) than those with pretreatment EBV-DNA≥2000 copies/ml, but there was no significant difference in OS (P= 0.062). Patients were divided into three groups by combination of ERCC1 mRNA and EBV-DNA level ERCC1 mRNA low expression/pre EBV-DNA<2000 copies/ml, ERCC1 mRNA low expression/pre EBV-DNA≥2000 copies/ml, ERCC1 mRNA high expression/pre EBV-DNA≥2000 copies/ml. In these groups, 1-year, 3-year, 5‐year OS were 100%, 100%, 100%; 100%, 94.1%, 90.9%; 100%, 85%, 72.9%, respectively (P=0.038); 1-year, 3-year, 5‐year PFS were 100%, 100%, 100%; 97.1%, 91.2%, 84.8%; 95%, 85%, 71.4%, respectively (P=0.028). Multivariate analysis showed combination of ERCC1 mRNA and EBV-DNA levels remained independent prognostic factor but not ERCC1 mRNA and EBV-DNA alone. Conclusion: Combined ERCC1 mRNA and pre EBV-DNA is a better prognostic factor in stage II NPC patients treated with concurrent chemoradiation. Patients with ERCC1 mRNA high expression/pre EBV-DNA≥2000 copies/ml should be treated with more aggressive regimen.