Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients

Abstract

Objective: Circulating cell-free Epstein-Barr virus (EBV) DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma (NPC). Despite important insights into the biology of persistence, few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells (PBCs).

Methods: A prospective observational cohort study was conducted involving 1,063 newly diagnosed, locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007. Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival (OS) and other prognostic outcomes. Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.

Results: After a median follow-up of 108 months, patients with higher PBC EBV-DNA loads had significantly worse OS [hazard ratio (HR) of medium, medium-high, and high vs. low were 1.50, 1.52, and 1.85 respectively; P_trend < 0.001]. Similar results were found for progression-free survival and distant metastasis-free survival. The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66, respectively. Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker, which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort (HR: 1.88; P = 0.025). Importantly, a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.

Conclusions: The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.

Keywords: Epstein-Barr virus DNA; Nasopharyngeal carcinoma; nomogram; peripheral blood cells; prognosis.

Figure 1

Kaplan-Meier survival curves of Epstein-Barr virus DNA in peripheral blood cells for (A) overall survival, (B) progression-free survival, (C) distant metastasis-free survival, and (D) recurrence-free survival in all patients.

Figure 2

Nomogram (A), including age, gender, education level, T stage, N stage, concurrent chemotherapy, body mass index, smoking status, serum lactate dehydrogenase levels, and neutrophil to lymphocyte ratio for 3-, 5-, and 10-year overall survival (OS) in patients with nasopharyngeal carcinoma. The calibration curve (B) of the nomogram for predicting OS. The Kaplan-Meier curves (C) of different risk groups in the training and validation sets according to the score system for the OS.

Figure 3

A scatter plot (A) indicating the correlation between plasma Epstein-Barr virus (EBV) DNA and peripheral blood cell (PBC) EBV DNA. Grep points are the jittered points. Kaplan-Meier survival curves of overall survival. (B) plasma EBV DNA alone, (C) PBC EBV DNA alone, (D) The combination of plasma EBV DNA and PBC EBV DNA.