title: Circulating Epstein-Barr virus microRNAs miR-BART7 and miR-BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment.
abstract: 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.
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Gaohong
authors.initials: G
authors.lastname: Zhang
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Zong
authors.forename: Shaojun
authors.initials: S
authors.lastname: Lin
authors.forename: Rob J A
authors.initials: RJ
authors.lastname: Verhoeven
authors.forename: Shuang
authors.initials: S
authors.lastname: Tong
authors.forename: Yixin
authors.initials: Y
authors.lastname: Chen
authors.forename: Mingfang
authors.initials: M
authors.lastname: Ji
authors.forename: Weimin
authors.initials: W
authors.lastname: Cheng
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Maria
authors.initials: M
authors.lastname: Lung
authors.forename: Jianji
authors.initials: J
authors.lastname: Pan
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002277:Carcinoma; D059248:Chemoradiotherapy; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000235:genetics* / Q000628:therapy / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000235:genetics* / Q000628:therapy / Q000821:virology; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000628:therapy / Q000821:virology; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: EBV BART; Epstein-Barr virus; NPC; biomarker; microRNA