Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Nobuyuki
N
Hirai
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Naohiro
N
Wakisaka
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Satoru
S
Kondo
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Mitsuharu
M
Aga
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Makiko
M
Moriyama-Kita
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Takayoshi
T
Ueno
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Yosuke
Y
Nakanishi
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Kazuhira
K
Endo
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Hisashi
H
Sugimoto
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Shigeyuki
S
Murono
Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
Hiroshi
H
Sato
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.
Tomokazu
T
Yoshizaki
Lancet Oncol. 2012 Jun;13(6):633-41
22560814
Virol J. 2013 Apr 16;10:119
23590857
Auris Nasus Larynx. 2011 Apr;38(2):244-9
20817430
Med Chem. 2006 Nov;2(6):555-63
17105436
Radiat Oncol. 2010 Mar 26;5:25
20346162
Auris Nasus Larynx. 2007 Mar;34(1):73-8
17129696
Laryngoscope. 2005 Aug;115(8):1517-9
16094136
J Pathol. 2012 Aug;227(4):392-403
22431062
Virology. 2009 Apr 10;386(2):387-97
19217135
PLoS One. 2008 Sep 22;3(9):e3254
18806872
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8
21383194
Virol J. 2010 Oct 15;7:271
20950422
BMC Cancer. 2015 Nov 06;15:862
26545861
Clin Cancer Res. 2003 Aug 15;9(9):3431-4
12960133
Cancer Res. 2007 Dec 1;67(23):11111-6
18056433
PLoS One. 2012;7(10):e46367
23056289
Clin Chem. 2014 May;60(5):773-82
24563490
Nat Rev Clin Oncol. 2011 Jun 07;8(8):467-77
21647195
Science. 2004 Apr 30;304(5671):734-6
15118162
Head Neck Pathol. 2007 Sep;1(1):81-6
20614287
Asian Pac J Cancer Prev. 2013;14(10):5637-44
24289555
Oral Oncol. 2014 Jun;50(6):527-38
24440146
Cancer Med. 2015 Aug;4(8):1186-95
25991077
Cancer. 2012 Feb 1;118(3):698-710
21720996
Jpn J Clin Oncol. 2015 Mar;45(3):244-7
25583421
Chin J Cancer. 2012 Mar;31(3):142-9
22237037
Curr Opin Virol. 2012 Aug;2(4):453-8
22858118
Cancer. 1971 Sep;28(3):566-70
5096921
Int J Radiat Oncol Biol Phys. 1981 Apr;7(4):447-53
6788731
N Engl J Med. 2004 Jun 10;350(24):2461-70
15190138
Semin Cancer Biol. 2014 Jun;26:52-9
24602823
Cancer Lett. 2013 Aug 28;337(1):1-7
23689138
Int J Cancer. 2015 Mar 1;136(5):E301-12
25213622
Cancer Sci. 2004 Jun;95(6):508-13
15182432
J Clin Oncol. 1998 Apr;16(4):1310-7
9552031
Int J Radiat Oncol Biol Phys. 1978 Mar-Apr;4(3-4):182-98
640889
Proteomics. 2013 May;13(10-11):1608-23
23505015
Cancer. 1988 Jun 1;61(11):2338-41
3365661
Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16164-9
17911266
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8
18663219