Epstein–Barr virus-positive gastric cancer [EBV (+) GC] is associated with EBV infection and is one of the GC subtypes defined by the Cancer Genome Atlas. EBV (+) GC has several distinct genomic or epigenomic features and clinicopathological characteristics compared with other molecular subtypes of GC. Here, we summarize the unique features of EBV (+) GC including the clinical and histopathological features, and discuss associated genetic and epigenetic aberrations. We also discuss noncoding RNAs [EBV-encoded RNAs and EBV-encoded microRNAs (miRNAs)] derived from EBV-infected cells, which have not been described in detail previously. These noncoding RNAs are defined by their roles; for example, EBV-encoded miRNAs play pivotal roles in oncogenesis and tumor progression in EBV (+) GC. We also discuss recent advances in therapeutic modalities for EBV (+) GC, as well as the potential of EBV infection as a predictive biomarker of the response to anti-PD-1 therapy with immune checkpoint inhibitors. We introduce our recent studies focusing on AT-rich interactive domain 1A gene mutations and programmed death ligand-1 overexpression/CD274 copy-number amplification, which are recurrently identified in EBV (+) GC. Finally, based on those findings, we propose potential therapeutic options using candidate-targeted therapies against EBV (+) GC.

Epstein-Barr 病毒阳性胃癌 [EBV (+) GC] 与 EBV 感染有关，是癌症基因组图谱定义的 GC 亚型之一。与 GC 的其他分子亚型相比，EBV (+) GC 具有几个不同的基因组或表观基因组特征和临床病理学特征。在这里，我们总结了 EBV (+) GC 的独特特征，包括临床和组织病理学特征，并讨论了相关的遗传和表观遗传异常。我们还讨论了源自 EBV 感染细胞的非编码 RNA [EBV 编码的 RNA 和 EBV 编码的 microRNA (miRNA)]，以前没有详细描述过。这些非编码 RNA 由它们的作用定义。例如，EBV 编码的 miRNA 在 EBV (+) GC 的肿瘤发生和肿瘤进展中起关键作用。我们还讨论了 EBV (+) GC 治疗方式的最新进展，以及 EBV 感染作为免疫检查点抑制剂抗 PD-1 治疗反应的预测生物标志物的潜力。我们介绍了我们最近的研究，重点是富含 AT 的交互域 1A 基因突变和程序性死亡配体 1 过表达/CD274拷贝数扩增，在 EBV (+) GC 中反复鉴定。最后，基于这些发现，我们提出了使用针对 EBV (+) GC 的候选靶向疗法的潜在治疗选择。