Shoda Katsutoshi, Ichikawa Daisuke, Fujita Yuji, Masuda Kiyoshi, Hiramoto Hidekazu, Hamada Junichi, Arita Tomohiro, Konishi Hirotaka, Kosuga Toshiyuki, Komatsu Shuhei, Shiozaki Atsushi, Okamoto Kazuma, Imoto Issei, Otsuji Eigo
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.
Oncotarget. 2017 Apr 25;8(17):28796-28804. doi: 10.18632/oncotarget.15675.
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.
近期对胃癌（GC）进行的全面分子亚型分析将爱泼斯坦-巴尔病毒（EBV）阳性肿瘤确定为具有独特显著分子和临床特征的一种亚型。在本研究中，我们旨在确定循环游离EBV DNA作为生物标志物在检测和/或监测EBV相关胃癌（EBVaGC）患者治疗反应方面的潜在效用。通过定量实时聚合酶链反应测定了153例GC患者的GC肿瘤和血浆样本中的EBV基因与核糖核酸酶P RNA组分H1的比率（EBV比率），其中包括14例通过传统方法诊断为EBVaGC的患者。在14例GC患者中检测到了循环游离EBV DNA：检测的敏感性和特异性分别为71.4%（10/14）和97.1%（135/139）。血浆EBV比率与EBVaGC肿瘤大小显著相关，并且EBVaGC病例术前检测到的血浆EBV DNA在术后消失。EBVaGC患者可能预后较好，但循环游离EBV DNA对预后无影响或影响很小。此外，对EBVaGC患者血浆EBV比率的重复评估显示，治疗后血浆EBV DNA减少，而在肿瘤进展/复发期间血浆EBV DNA增加。这些结果表明，循环游离DNA在揭示EBV DNA以鉴定EBVaGC亚型和/或实时监测EBVaGC患者的肿瘤进展以及治疗反应方面具有潜在效用。
