Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with gastric cancer.
Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with gastric cancer.
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DOI：
10.18632/oncotarget.15675
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发表时间：
2017-04-25
期刊：
影响因子：
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通讯作者：
Otsuji E
中科院分区：
文献类型：
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作者：
Shoda K;Ichikawa D;Fujita Y;Masuda K;Hiramoto H;Hamada J;Arita T;Konishi H;Kosuga T;Komatsu S;Shiozaki A;Okamoto K;Imoto I;Otsuji E
最近的胃癌（GC）的综合分子亚型确定EB病毒（EBV）阳性的肿瘤作为一个亚型，具有独特的显着的分子和临床特征。在这项研究中，我们的目的是确定循环无细胞EBV DNA作为检测和/或监测EBV相关胃癌（EBVaGC）患者治疗反应的生物标志物的潜在效用。应用实时定量聚合酶链反应（PCR）技术检测了153例胃癌患者（包括14例经常规方法确诊的EBVaGC患者）的肿瘤和血浆中EBV基因与核糖核酸酶P RNA组分H1的比值（EBV比值）。检测14例胃癌患者循环游离EBV DNA，其敏感性和特异性分别为71.4%（10/14）和97.1%（135/139）。血浆EBV比值与EBVaGC肿瘤大小显著相关，EBVaGC患者术前检测到的血浆EBV DNA在手术后消失。EBVaGC患者可能有较好的预后，但循环无细胞EBV DNA对预后没有或影响很小。此外，EBVaGC中血浆EBV比率的重复评估分别显示治疗后和肿瘤进展/复发期间血浆EBV DNA减少和增加。这些结果表明，循环无细胞DNA的潜在效用，揭示EBV DNA的EBVaGC亚型的鉴定和/或实时监测肿瘤进展以及治疗反应的患者与EBVaGC。
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.