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

• Published in: Cancer science Vol. 111; no. 5; pp. 1711 - 1723
• Main Authors: Lu, Tianzhu, Guo, Qiaojuan, Lin, Keyu, Chen, Honglin, Chen, Yixin, Xu, Yuanji, Lin, Cheng, Su, Ying, Chen, Yan, Chen, Mengyuan, Zheng, Yuhong, Ye, Yunbin, Lin, Shaojun, Zong, Jingfeng, Pan, Jianji
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2020; John Wiley and Sons Inc
• Subjects: Asymptomatic; biomarker; Biomarkers; Cancer; Chemotherapy; Deoxyribonucleic acid; DNA; Epstein-Barr virus; Medical prognosis; Metastases; Metastasis; microRNA; MicroRNAs; miRNA; Nasopharyngeal carcinoma; Original; Plasma; Plasma levels; Radiation therapy; Software; Tumors; China; microRNA; nasopharyngeal carcinoma; Epstein-Barr virus; biomarker; metastasis
• DOI: 10.1111/cas.14381
• ISSN: 1347-9032; 1349-7006

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‐naïve 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. This is so far the most extensive retrospective study to report the diagnostic and prognostic value of circulating levels of the Epstein‐Barr virus BamHI A rightward transcripts encoded microRNAs (EBV miR‐BARTs) in nasopharyngeal carcinoma. Compared with circulating EBV DNA, this study found that circulating EBV miR‐BARTs is not inferior to EBV DNA in diagnosis and prognosis. Furthermore, the combination of circulating levels of EBV DNA and miR‐BARTs at diagnosis can improve the potential for diagnostic and prognostic evaluation.