Establishment of a Screening Method for Epstein-Barr Virus-Associated Gastric Carcinoma by Droplet Digital PCR.

Epstein-Barr virus droplet digital PCR endoscopic biopsy gastric carcinoma

Journal

Microorganisms
ISSN: 2076-2607
Titre abrégé: Microorganisms
Pays: Switzerland
ID NLM: 101625893

Informations de publication

Date de publication:
29 Nov 2019
Historique:
received: 28 10 2019
revised: 26 11 2019
accepted: 28 11 2019
entrez: 5 12 2019
pubmed: 5 12 2019
medline: 5 12 2019
Statut: epublish

Résumé

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is classified as one of the molecular subtypes of gastric cancer. We used droplet digital polymerase chain reaction (ddPCR) to enable highly sensitive and quantitative detection of EBV. EBV-DNA load was calculated based on the copy number of the BamH1-W fragment of EBV by ddPCR, and the cut-off value of EBV-DNA load was set. We conducted both ddPCR and EBER1 ISH to examine whether their results coincided in 158 gastric cancer specimens of unknown EBV status. We prepared 26 biopsy specimens and 49 serum samples including EBVaGC and assayed them by ddPCR. The median values of EBV-DNA load for EBVaGC and EBV-negative control were 17.0 and 0.00308, respectively. A cut-off value of 0.032 was determined for which the sensitivity was 1. Among the 158 gastric cancer specimens, 14 lesions were judged as EBV-positive by the 0.032 cut-off value determined by ddPCR. The results of ddPCR and EBER1 ISH were in complete agreement. Even when using a biopsy specimen as a sample for ddPCR, the EBV-DNA load of all EBVaGCs was larger than the cut-off value. We established a new method of diagnosing EBVaGC from tissue samples by ddPCR.

Sections du résumé

BACKGROUND BACKGROUND
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is classified as one of the molecular subtypes of gastric cancer. We used droplet digital polymerase chain reaction (ddPCR) to enable highly sensitive and quantitative detection of EBV.
METHODS METHODS
EBV-DNA load was calculated based on the copy number of the BamH1-W fragment of EBV by ddPCR, and the cut-off value of EBV-DNA load was set. We conducted both ddPCR and EBER1 ISH to examine whether their results coincided in 158 gastric cancer specimens of unknown EBV status. We prepared 26 biopsy specimens and 49 serum samples including EBVaGC and assayed them by ddPCR.
RESULTS RESULTS
The median values of EBV-DNA load for EBVaGC and EBV-negative control were 17.0 and 0.00308, respectively. A cut-off value of 0.032 was determined for which the sensitivity was 1. Among the 158 gastric cancer specimens, 14 lesions were judged as EBV-positive by the 0.032 cut-off value determined by ddPCR. The results of ddPCR and EBER1 ISH were in complete agreement. Even when using a biopsy specimen as a sample for ddPCR, the EBV-DNA load of all EBVaGCs was larger than the cut-off value.
CONCLUSIONS CONCLUSIONS
We established a new method of diagnosing EBVaGC from tissue samples by ddPCR.

Identifiants

pubmed: 31795435
pii: microorganisms7120628
doi: 10.3390/microorganisms7120628
pmc: PMC6956032
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 18K07974

Déclaration de conflit d'intérêts

The authors declare no financial or commercial conflicts of interest.

Références

Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Int J Gastrointest Cancer. 2003;34(2-3):87-94
pubmed: 15361640
N Engl J Med. 2017 Aug 10;377(6):513-522
pubmed: 28792880
Am J Pathol. 1993 Nov;143(5):1250-4
pubmed: 8238241
Nature. 2014 Sep 11;513(7517):202-9
pubmed: 25079317
Nat Med. 2018 Sep;24(9):1449-1458
pubmed: 30013197
Cancer. 1994 May 1;73(9):2239-49
pubmed: 8168030
Clin Cancer Res. 2011 May 1;17(9):2885-92
pubmed: 21478335
Am J Pathol. 1992 Apr;140(4):769-74
pubmed: 1314023
Nature. 1970 Dec 12;228(5276):1056-8
pubmed: 4320657
J Mol Diagn. 2004 Nov;6(4):378-85
pubmed: 15507678
Gastroenterology. 2009 Sep;137(3):824-33
pubmed: 19445939
Int J Cancer. 2020 Jan 1;146(1):272-280
pubmed: 31162842
Anal Chem. 2011 Nov 15;83(22):8604-10
pubmed: 22035192
Clin Cancer Res. 2001 Jul;7(7):1856-9
pubmed: 11448896
Am J Pathol. 1993 Oct;143(4):1063-71
pubmed: 8214002
Mod Pathol. 1990 May;3(3):377-80
pubmed: 2163534
Ann Clin Biochem. 2017 Jan;54(1):86-91
pubmed: 27126270
Am J Pathol. 1991 Sep;139(3):469-74
pubmed: 1653517
Cancer. 1996 May 15;77(10):1998-2004
pubmed: 8640662
Oncotarget. 2017 Apr 25;8(17):28796-28804
pubmed: 28430637
J Med Virol. 2001 Oct;65(2):348-57
pubmed: 11536243
Lancet. 2017 Dec 2;390(10111):2461-2471
pubmed: 28993052
Cancers (Basel). 2018 May 29;10(6):null
pubmed: 29843478

Auteurs

Takuya Shuto (T)

Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Jun Nishikawa (J)

Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Kanami Shimokuri (K)

Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Ayaka Yanagi (A)

Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Tatsuya Takagi (T)

Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Fumiya Takagi (F)

Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Osamu Miura (O)

Hofu Institute of Gastroenterology, 14-33 Ekiminami-machi, Hofu, Yamaguchi 747-0801, Japan.

Michihisa Iida (M)

Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Hiroaki Nagano (H)

Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Yoshihiro Takemoto (Y)

Department of Clinical Science of Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Eijiro Harada (E)

Department of Clinical Science of Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Yutaka Suehiro (Y)

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Takahiro Yamasaki (T)

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Takeshi Okamoto (T)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Isao Sakaida (I)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

Classifications MeSH