Our series of NPC patients was obviously too heterogeneous to attempt correlations between the concentration of plasma miR-BART17 and clinical parameters. However, we were able to collect sequential plasma samples selleck inhibitor for one patient (Patient n��5) who had a rapidly progressive disease. We observed a dramatic increase in the concentration of miR-BART17 which was parallel to tumor progression. This suggests that the plasma concentration of miR-BART17 is related, at least in part, to the tumor mass. That point will require further investigations. In this small series, we have found no obvious correlations between the concentrations of plasma miR-BART17 and the plasma EBV DNA loads.

One can speculate that both miR-BART and EBV DNA plasma copy numbers are affected by multiple factors: the total tumor burden, the apoptotic index of the malignant cells, their rate of necrosis, the vascularization of tumor lesions and the rate of degradation of microRNAs and DNA by peripheral nucleases. However, the relative impact of each of these factors is probably different for the miR-BARTs and for the EBV-DNA. This could explain why their plasma concentrations might evolve independently at various stages of the disease. On the other hand, if the concentrations of miR-BARTs and EBV DNA are at least partially independent, they have more chances to provide non-redundant information for assessment of the tumor status and/or prediction of the tumor evolution.

In order to substantiate this hypothesis, we currently investigate: 1) the relationships between the abundance of circulating miR-BARTs and the total tumor mass in a series of non-metastatic NPC patients; 2) the longitudinal evolution of circulating miR-BARTs in connection with the tumor response to the initial treatment. While this study was near completion, Chan et al. have reported a consistent detection of miR-BART7 in the plasma of NPC patients [23]. Both studies converge on two important points: 1) EBV BART microRNAs are detectable in the plasma of some non-NPC donors but at a low level in contrast with most NPC patients; 2) the concentration of circulating miR-BARTs seems to be relatively independent of the plasma viral DNA load. Conclusions This study confirms the consistent and specific presence of a circulating miR-BART in plasma samples from NPC patients.

We provide evidence that the concentration of plasma miR-BART17 is, at least in part, independent of the Entinostat plasma viral DNA load. In addition, we show that this microRNA is not bound to plasma exosomes but probably associated to non-vesicular ribonucleoprotein complexes. These observations will provide a basis to address questions about the relationship of plasma miR-BARTs with NPC volumetric characteristics and about their possible role in the prediction of tumor response under treatment.