Research Papers:

Clinical utility of circulating cell-free Epstein–Barr virus DNA in patients with gastric cancer

Katsutoshi Shoda, Daisuke Ichikawa _, Yuji Fujita, Kiyoshi Masuda, Hidekazu Hiramoto, Junichi Hamada, Tomohiro Arita, Hirotaka Konishi, Toshiyuki Kosuga, Shuhei Komatsu, Atsushi Shiozaki, Kazuma Okamoto, Issei Imoto and Eigo Otsuji

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Oncotarget. 2017; 8:28796-28804. https://doi.org/10.18632/oncotarget.15675

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Katsutoshi Shoda1, Daisuke Ichikawa1, Yuji Fujita1,2, Kiyoshi Masuda2, Hidekazu Hiramoto1, Junichi Hamada1, Tomohiro Arita1, Hirotaka Konishi1, Toshiyuki Kosuga1, Shuhei Komatsu1, Atsushi Shiozaki1, Kazuma Okamoto1, Issei Imoto2, Eigo Otsuji1

1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan

2Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan

Correspondence to:

Daisuke Ichikawa, email: ichikawa@koto.kpu-m.ac.jp

Issei Imoto, email: issehgen@tokushima-u.ac.jp

Keywords: gastric cancer, Epstein–Barr virus, liquid biopsy

Received: October 29, 2016    Accepted: February 6, 2017    Published: February 24, 2017


Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein–Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method. Circulating cell-free EBV DNA was detected in 14 patients with GC: the sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis. In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and increase in plasma EBV DNA after treatment and during tumor progression/recurrence, respectively. These results suggest the potential utility of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC subtype and/or for real-time monitoring of tumor progression as well as treatment response in patients with EBVaGC.

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