Serologic Antienzyme Rate of Epstein-Barr Virus DNase-Specific Neutralizing Antibody Segregates TNM Classification in Nasopharyngeal Carcinoma

Abstract

Purpose We investigate the value of pretreatment serologic antienzyme rate (AER) of Epstein-Barr virus (EBV) DNase-specific neutralizing antibody complementing TNM staging in prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods Pretreatment serum samples from 1,303 patients with untreated NPC were collected and examined for AER. After a 10-year follow-up period, the prognoses of the patients, classified by their clinical stage with AER, were assessed by multivariate analysis. Of the 1,303 patients, 600 patients were randomly assigned to a training set to generate an AER cutoff point by receiver operating characteristic (ROC) curve analysis. AER levels were then analyzed with overall survival (OS), progression-free survival (PFS), local failure–free survival (LFFS), and distant metastasis–free survival (DMFS) in a testing set (703 patients). Another independent cohort of 464 patients was studied in a validating set. Results In the training set, the ROC analysis–generated AER cutoff point for OS was 58.0%, which was used as the cutoff point in the testing set. The subset of low AER levels predicted a significant survival advantage over the subset of high AER levels for OS, PFS, LFFS, and DMFS in the testing set. Moreover, two distinguished subgroups were segregated by an AER level of 58.0% within each clinical stage comparing prognostication of OS, PFS, LFFS, and DMFS. Importantly, AER level was revealed as the only significant independent prognostic factor for death, recurrence, and distant metastasis in the validating set. Conclusion Pretreatment serologic AER of EBV DNase-specific neutralizing antibody serves as an independent prognostic marker complementing TNM stage in NPC. Supplementing pretreatment AER with TNM staging leads to more accurate risk definition in patient subgroups.