Circulating Epstein-Barr virus microRNAs BART7-3p and BART13-3p as novel biomarkers in nasopharyngeal carcinoma

Epstein-Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV-miR-BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naive NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV DNA were independent risk for shorter distant metastasis-free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44-5.97, P = .003; HR = 2.27, 95% CI, 1.26-4.10, P = .006) in multivariate Cox regression. Epstein-Barr virus DNA, miR-BART7-3p, and miR-BART13-3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR-BART7-3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89-9.01, P < .001; HR = 2.14, 95% CI, 1.04-4.42, P = .039). The 4-year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR-BART7-3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR-BART7-3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR-BART7-3p and EBV DNA after radiotherapy (P < .001). Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS.