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 5 89), and healthy (n 5 28) and non-NPC tumor patient controls (n 5 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.

MicroRNAs of Epstein-Barr Virus Control Innate and Adaptive Antiviral Immunity

“…Circulating miRNAs of EBV have been proposed to serve as diagnostic markers in patients with nasopharyngeal carcinoma, for example (34).…”

Abnormally expressed microRNA as auxiliary biomarkers for nasopharyngeal carcinoma: A meta‑analysis

“…For example, a previous study has demonstrated that miRNA testing is adequately sensitive and specific for NPC confirmation, with a diagnostic sensitivity and specificity of up to 96% (13). However, some research has reported that miRNA testing achieved an efficacy <60% (10,14,15). Therefore, the present study conducted a comprehensive meta-analysis and aimed to assess the overall diagnostic performance of miRNA as biomarkers for NPC identification.…”

“…Numerous studies have documented that deregulated miRNA expression is strongly linked to the occurrence of various carcinomas (7,8). It has become increasingly apparent that miRNA are of crucial importance for the carcinogenesis and progression of NPC, and therefore they have been highlighted as powerful screening predictors in confirming or monitoring NPC (9)(10)(11)(12)(13)(14)(15). Unfortunately, the clinical utility of miRNA signatures remain unpopular in the clinic.…”

Exosomes as the Promising Biomarker for Epstein-Barr Virus (EBV)-Associated Cancers

“…In addition, other pathogenic factors that are enriched in EBV exosomes such as EBV DNAs, EBV mRNAs and EBV miRNAs have also been shown to be potential biomarkers for EBV cancer diagnosis [56][57][58][59] ( Table 2). Using quantitative PCR (qPCR), Yip and colleagues showed that high-EBV DNAs could be detected in plasma/serum of NPC patients at late stages of disease and the viral loads were associated with poor survival or frequent relapse in NPC patients [56,59].…”

“…On the other hand, Zhang and co-workers showed that EBV miRNAs (miR-BART7 and miR-BART13) can serve as important biomarkers for NPC diagnosis and prediction of treatment efficacy [58]. The potential prognostic value of EGFR and HIF1α has been previously demonstrated in breast and prostate cancers [60,61].…”