Virology and Cancer Research Unit, Children's Hospital of Mexico Federico Gomez, Mexico City, 06720, Mexico.
Curr Cancer Drug Targets. 2017;17(6):534-554. doi: 10.2174/1568009616666160926124923.
EBV-associated Gastric Cancer (EBVaGC) comprises about 9% of all cases of GC and constitutes a distinct clinicopathological and molecular entity. The pattern of viral expression in EBVaGC cannot be set to any of the previously EBV-associated malignancies. Several lines of evidence support that viral expression in EBVaGC is characterized by high transcription of the BamH1- A rightward transcript (BART), low-levels of EBNA-1 and lack of LMP1. The high transcription activity of the BamH1-A region is importantly directed to express BART miRNAs, supporting a critical role for these miRNAs during epithelial cell infection and carcinogenesis. Several studies have shown that promoter hypermethylation is also a prominent feature of EBVaGC. Based on the recent TCGA report, the specific fingerprint of genomic alterations in EBVaGC is marked by mutations in PIK3CA, ARID1A and BCOR genes, and amplification of 9p24.1 that harbors the genes for the JAK2, PD-L1 and PD-L2 proteins. The specific programs of viral gene expression, promoter methylation and genomic mutations found in EBVaGC target cell signaling pathways leading to increased proliferation, increased cell survival, immune evasion, augmented EMT and acquisition of stemness features. Less understood is the participation of EBV in chronic gastric inflammation, but some studies argue that EBV, similar to and together with Helicobacter pylori, is an early participant in the GC oncogenic process through promoting chronic inflammation and increased tissue damage.
Here, we discuss the principal and distinctive carcinogenic routes promoted by EBV in the gastric epithelium.
EBV 相关胃癌（EBVaGC）约占所有 GC 的 9%，构成了一种独特的临床病理和分子实体。EBVaGC 中的病毒表达模式不能归结于任何先前 EBV 相关的恶性肿瘤。有几条证据表明，EBVaGC 中的病毒表达以 BamH1-A 右向转录物（BART）的高转录、低水平的 EBNA-1 和缺乏 LMP1 为特征。BamH1-A 区域的高转录活性重要地定向表达 BART miRNAs，这支持这些 miRNAs 在上皮细胞感染和癌变过程中发挥关键作用。几项研究表明，启动子甲基化也是 EBVaGC 的一个突出特征。基于最近 TCGA 的报告，EBVaGC 中基因组改变的特定特征是 PIK3CA、ARID1A 和 BCOR 基因的突变以及 9p24.1 的扩增，该区域包含 JAK2、PD-L1 和 PD-L2 蛋白的基因。在 EBVaGC 中发现的病毒基因表达、启动子甲基化和基因组突变的特定程序靶向细胞信号通路，导致增殖增加、细胞存活增加、免疫逃逸、增强 EMT 和获得干性特征。不太清楚的是 EBV 在慢性胃炎症中的参与，但一些研究认为，EBV 类似于并与幽门螺杆菌一起，通过促进慢性炎症和增加组织损伤，成为 GC 致癌过程中的早期参与者。
在这里，我们讨论了 EBV 在胃上皮中促进的主要和独特的致癌途径。
