Abstract
ObjectivesEpstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p as well as BamHI-W DNA as biomarkers.Materials and MethodsSerums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients.ResultsThe sensitivity/specificity of circulating BamHI-W DNA, miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100 / 100, 85 / 85, 60 / 95, and 25 / 100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post-treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors.ConclusionThe copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis.
Highlights
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia, but rare in most countries including Japan [1,2,3]
Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis
Copy numbers of circulating BamHI-W DNA and the three BamHI-A rightward transcript (BART)-miRNAs for each NPC patient before and after treatment are summarized in S1 Table
Summary
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia, but rare in most countries including Japan [1,2,3]. In addition to its geographic and population variations, NPC has some unique features. Latent infection by Epstein-Barr virus (EBV) causes most cases of the non-keratinizing carcinoma differentiated type and non-keratinizing carcinoma undifferentiated type of NPCs, categorized as World Health Organization (WHO)-2A or WHO2B NPC [4]. Radiotherapy plays a central role in the locoregional control of NPC [9,10]. Another characteristic of NPC is that metastasis to regional and/or distant sites is more common than for other carcinomas of the head and neck. Chemotherapy plays an important role in improving the treatment outcome [11]
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