Specific detection of Epstein-Barr virus microRNAs in plasma samples from nasopharyngeal carcinoma patients: Correlation with tumor mass assessed by MRI.

Abstract

6079 Background: Epstein-Barr virus (EBV) microRNAs of the BART family can be detected in the plasma of at least a fraction of nasopharyngeal carcinoma (NPC) patients. Our aim was to investigate the specificity of plasma BART detection in NPC patients and the correlation with viral DNA load and/or clinical characteristics. Methods: Hsa miR484 and 4 miR-BARTs (ebv-miR BART 2-5p, 5, 9 and 18) were assessed by RT-PCR following RNA extraction in 37 plasma samples including 20 NPC, 8 non-NPC head and neck squamous cell carcinoma (SCC) patients and 9 healthy EBV carriers. EBV DNA copy numbers (viral load) were measured in the same samples. To explore correlations of BART concentrations with tumor mass, MRI-based volume analysis was designed and performed on a subset of 13 patients with non metastatic NPC. In addition, longitudinal variations of BART concentrations were studied in 9 NPC patients for whom we had sequential plasma samples. Results: The cellular hsa miR-484 was detected in all plasma samples with a slightly higher average concentration in plasma samples from NPC and SCC patients. On the other hand, the miR-BARTs were undetectable or at a very low level in samples from SCC patients and healthy carriers contrasting with a high level in most NPC patients. There was an overall positive correlation between EBVDNA copy numbers and plasma concentrations of each miR-BART. However substantial amounts of plasmatic miR-BARTs were observed in several patients for whom no plasma EBV DNA was detected.Their concentration was apparently not correlated to the initial tumor volume but their longitudinal variations were parallel with clinical evolution in all but one case. Conclusions: To a large extent, detection of plasma miR-BART-2-5p, 5, 9, and 18 is specific of NPC patients. Their concentration does not seem to correlate with tumor mass, at least in localized NPC patients. In a fraction of patients without initial detection of plasma EBV DNA, the kinetics of plasma BARTs may provide informations on early tumor response under treatment and may have prognostic value.