Open AccessPotential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma
Author(s) -
Nobuyuki Hirai,
Naohiro Wakisaka,
Satoru Kondo,
Mitsuharu Aga,
Makiko MoriyamaKita,
Takayoshi Ueno,
Yosuke Nakanishi,
Kazuhira Endo,
Hisashi Sugimoto,
Shigeyuki Murono,
Hiroshi Sato,
Tomokazu Yoshizaki
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0163609
Subject(s) - bamhi , nasopharyngeal carcinoma , microrna , biomarker , stage (stratigraphy) , virus , epstein–barr virus , medicine , gastroenterology , biology , cancer research , virology , genome , gene , genetics , radiation therapy , paleontology
Objectives Epstein-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 Methods Serums 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. Results The 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. Conclusion The 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.