Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

• Published in: International journal of cancer Vol. 136; no. 5; pp. E301 - E312
• Main Authors: Zhang, Gaohong, Zong, Jingfeng, Lin, Shaojun, Verhoeven, Rob J.A., Tong, Shuang, Chen, Yixin, Ji, Mingfang, Cheng, Weimin, Tsao, Sai‐Wah, Lung, Maria, Pan, Jianji, Chen, Honglin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2015
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; biomarker; Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cancer; Carcinoma; Chemoradiotherapy; EBV BART; Epstein-Barr virus; Epstein-Barr Virus Infections - blood; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - therapy; Epstein-Barr Virus Infections - virology; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Herpesvirus 4, Human - genetics; Humans; Lymphatic Metastasis; Male; Medical diagnosis; Medical research; microRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - blood; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - therapy; Nasopharyngeal Neoplasms - virology; Neoplasm Invasiveness; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - therapy; Neoplasm Recurrence, Local - virology; Neoplasm Staging; NPC; Prognosis; Radiation therapy; Reverse Transcriptase Polymerase Chain Reaction; Throat cancer; Viral Load; Young Adult; NPC; microRNA; Epstein-Barr virus; biomarker; EBV BART
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.29206

More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein–Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV‐harboring NPC and noncancerous NP cells found that miR‐BART3, miR‐BART7 and miR‐BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n = 89), and healthy (n = 28) and non‐NPC tumor patient controls (n = 18) found levels of both miR‐BART7 and miR‐BART13, but not miR‐BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR‐BART7 and miR‐BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR‐BART7 and miR‐BART13, but not miR‐BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR‐BART7 and miR‐BART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy. What's new? Nasopharyngeal carcinoma (NPC) is an Epstein‐Barr virus (EBV)‐associated tumor in which only a few viral proteins but more than 20 BART microRNAs are detected, at abundant levels. A systematic selection of extracellular BART microRNAs and evaluation of their usefulness as novel serological markers for NPC using clinical specimens is yet to be described. Here, the authors found that miR‐BART7 and miR‐BART13 are secreted from NPC cells into the bloodstream, with reduced plasma levels in NPC patients immediately after radiotherapy. These novel biomarkers for NPC malignancy warrant further evaluation for application in early recognition of disease onset and monitoring of treatment.