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Background Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized. Material and Methods We quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups. Results Plasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P =.001 or HR 2.74, 95% CI 1.27-5.91, P =.010), DMFS (HR 2.82, 95% CI 1.36-5.85, P =.005 or HR 3.27, 95% CI 1.57-6.81, P =.002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P =.018 or HR 2.03, 95% CI 1.14-3.62, P =.016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P =.070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis. Conclusion Plasma BART8-3p is a promising biomarker for the detection and prognosis of NPC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Metastasis is a major cause of death from malignant diseases, and the underlying mechanisms are still largely not known. A detailed probe into the factors which may regulate tumour invasion and metastasis contributes to novel anti-metastatic therapies. We previously identified a novel metastasis-associated gene 1 ( mag-1) by means of metastatic phenotype cloning. Then we characterized the gene expression profile of mag-1 and showed that it promoted cell migration, adhesion and invasion in vitro. Importantly, the disruption of mag-1 via RNA interference not only inhibited cellular metastatic behaviours but also significantly reduced tumour weight and restrained mouse breast cancer cells to metastasize to lungs in spontaneous metastatic assay in vivo. Furthermore, we proved that mag-1 integrates dual regulating mechanisms through the stabilization of HIF-1α and the activation of m TOR signalling pathway. We also found that mag-1-induced metastatic promotion could be abrogated by m TOR specific inhibitor, rapamycin. Taken together, the findings identified a direct role that mag-1 played in metastasis and implicated its function in cellular adaptation to tumour microenvironment. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], the authors reported two errors in the article. In the caption of Figure 1c the sentence "The 20 most highly upregulated EBV BART miRNAs identified between NPC specimens and normal nasopharyngeal mucosal specimens" should be corrected as "The highly upregulated EBV BART miRNAs identified between NPC specimens and normal nasopharyngeal mucosal specimens". [ABSTRACT FROM AUTHOR]