1. Circulating<scp>E</scp>pstein–<scp>B</scp>arr virus micro<scp>RNA</scp>s mi<scp>R‐BART7</scp>and mi<scp>R‐BART13</scp>as biomarkers for nasopharyngeal carcinoma diagnosis and treatment
- Author
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Shaojun Lin, Jingfeng Zong, Weimin Cheng, Rob J. A. Verhoeven, Shuang Tong, Maria Lung, Jianji Pan, Honglin Chen, Sai Wah Tsao, Mingfang Ji, Yixin Chen, and Gaohong Zhang
- Subjects
Adult ,Male ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Cancer Research ,Adolescent ,medicine.medical_treatment ,Biology ,medicine.disease_cause ,Virus ,Young Adult ,Antineoplastic Combined Chemotherapy Protocols ,microRNA ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,Neoplasm Invasiveness ,Aged ,Neoplasm Staging ,Nasopharyngeal Carcinoma ,Reverse Transcriptase Polymerase Chain Reaction ,Carcinoma ,Nasopharyngeal Neoplasms ,Chemoradiotherapy ,Middle Aged ,Viral Load ,Prognosis ,medicine.disease ,Epstein–Barr virus ,Gene Expression Regulation, Neoplastic ,Radiation therapy ,MicroRNAs ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Cell culture ,Lymphatic Metastasis ,Serological biomarkers ,Immunology ,Cancer research ,Biomarker (medicine) ,Female ,Neoplasm Recurrence, Local ,Follow-Up Studies - 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.
- Published
- 2014