scholarly journals Clinical Importance of Epstein–Barr Virus-Associated Gastric Cancer

Cancers ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 167 ◽  
Author(s):  
Jun Nishikawa ◽  
Hisashi Iizasa ◽  
Hironori Yoshiyama ◽  
Kanami Shimokuri ◽  
Yuki Kobayashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Low Frequency ◽  
Clinical Importance ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr

Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is the most common malignancy caused by EBV infection. EBVaGC has definite histological characteristics similar to gastric carcinoma with lymphoid stroma. Clinically, EBVaGC has a significantly low frequency of lymph node metastasis compared with EBV-negative gastric cancer, resulting in a better prognosis. The Cancer Genome Atlas of gastric adenocarcinomas proposed a molecular classification divided into four molecular subtypes: (1) EBVaGC; (2) microsatellite instability; (3) chromosomal instability; and (4) genomically stable tumors. EBVaGC harbors a DNA methylation phenotype, PD-L1 and PD-L2 overexpression, and frequent alterations in the PIK3CA gene. We review clinical importance of EBVaGC and discuss novel therapeutic applications for EBVaGC.

scholarly journals Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer

2020 ◽  
Vol 8 (2) ◽  
pp. 258 ◽  
Author(s):  
Jae Hee Yoon ◽  
Kyoungmi Min ◽  
Suk Kyeong Lee
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Ags Cells ◽  
Anchorage Independent Growth ◽  
Barr Virus ◽  
Epstein Barr ◽  
Bart Mirnas

Epstein-Barr virus (EBV) infects more than 90% of the global population and is associated with a variety of tumors including nasopharyngeal carcinoma, Hodgkin lymphoma, natural killer/T lymphoma, and gastric carcinoma. In EBV-associated gastric cancer (EBVaGC), highly expressed EBV BamHI A rightward transcripts (BART) miRNAs may contribute to tumorigenesis with limited viral antigens. Despite previous studies on the targets of BART miRNAs, the functions of all 44 BART miRNAs have not been fully clarified. Here, we used RNA sequencing data from the Cancer Genome Atlas to find genes with decreased expression in EBVaGC. Furthermore, we used AGS cells infected with EBV to determine whether expression was reduced by BART miRNA. We showed that the expression of Kruppel-like factor 2 (KLF2) is lower in AGS-EBV cells than in the AGS control. Using bioinformatics analysis, four BART miRNAs were selected to check whether they suppress KLF2 expression. We found that only miR-BART17-5p directly down-regulated KLF2 and promoted gastric carcinoma cell migration and anchorage-independent growth. Our data suggest that KLF2 functions as a tumor suppressor in EBVaGC and that miR-BART17-5p may be a valuable target for effective EBVaGC treatment.

scholarly journals MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link with Novel Immunotherapy

2020 ◽  
Vol 9 (5) ◽  
pp. 1427 ◽  
Author(s):  
Maria Grazia Rodriquenz ◽  
Giandomenico Roviello ◽  
Alberto D’Angelo ◽  
Daniele Lavacchi ◽  
Franco Roviello ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Chromosomal Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Gastric Cancers ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Genome Atlas

Gastric cancers have been historically classified based on histomorphologic features. The Cancer Genome Atlas network reported the comprehensive identification of genetic alterations associated with gastric cancer, identifying four distinct subtypes— Epstein-Barr virus (EBV)-positive, microsatellite-unstable/instability (MSI), genomically stable and chromosomal instability. In particular, EBV-positive and MSI gastric cancers seem responsive to novel immunotherapies drugs. The aim of this review is to describe MSI and EBV positive gastric cancer’s subgroups and their relationship with novel immunotherapy.

scholarly journals PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroshi Nakano ◽  
Motonobu Saito ◽  
Shotaro Nakajima ◽  
Katsuharu Saito ◽  
Yuko Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epstein Barr Virus ◽  
Tumor Tissue ◽  
The Cancer Genome Atlas ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Dual Mechanism ◽  
Irf3 Activation

AbstractEpstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (−) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3.

scholarly journals Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas

2015 ◽  
Vol 19 (2) ◽  
pp. 676-681 ◽  
Author(s):  
M. Constanza Camargo ◽  
Reanne Bowlby ◽  
Andy Chu ◽  
Chandra Sekhar Pedamallu ◽  
Vesteinn Thorsson ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Next Generation Sequencing ◽  
Epstein Barr Virus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Generation Sequencing ◽  
Genome Atlas

scholarly journals Epstein-Barr Virus-associated Gastric Carcinoma

2021 ◽  
Vol 21 (1) ◽  
pp. 22-28
Author(s):  
Bong Eun Lee
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Barr Virus ◽  
Node Metastasis ◽  
Epstein Barr

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) comprises approximately 10% of all gastric cancers and is now defined as one of the four subtypes of gastric cancer according to the molecular classification proposed by the Cancer Genome Atlas project. EBVaGC has characteristic genetic profiles that harbor a DNA methylation phenotype, frequent mutations in PIK3CA and ARID1A, and amplification of JAK2 and programmed death-ligand (PD-L)1/PD-L2. Therefore, EBVaGC shows several distinct clinicopathological features, including a male predominance, proximal stomach location, gastric carcinoma with lymphoid stroma histology, low risk of lymph node metastasis, and favorable prognosis. In clinical practice, patients with early EBVaGC might be good candidates for endoscopic resection or minimally invasive surgery since the rate of lymph node metastasis is very low, even with deep submucosal invasion. Furthermore, in the case of advanced EBVaGC, the applicability of immunotherapy has been investigated based on its increased expression of PD-L1 and high immunogenicity. In conclusion, EBV can serve as a biomarker in gastric cancer, and further identification of other molecular characteristics of EBVaGC is essential for new potential therapeutic targets.

scholarly journals Epstein-Barr Virus-Associated Gastric Cancer: Old Entity with New Relevance

2021 ◽  
Author(s):  
Hugo Manuel Lopes de Sousa ◽  
Joana Patrícia Costa Ribeiro ◽  
Mafalda Basílio Timóteo
Keyword(s):  
Gastric Cancer ◽  
Epstein Barr Virus ◽  
The Cancer Genome Atlas ◽  
Public Health Issue ◽  
Tumor Subtype ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Meta Analyses ◽  
Genome Atlas

Gastric cancer (GC) represents a major public health issue worldwide, being the fifth most common cancer and one of the leading causes of death by cancer. In 2014, The Cancer Genome Atlas (TCGA) established that tumors positive for Epstein-Barr virus (EBV) are considered a specific subtype of GC (EBVaGC). Several meta-analyses have shown that EBVaGC represents almost 10% of all gastric cancer worldwide, with small differences in the geographic distribution. This tumor subtype has a high potential of being clinically relevant and studies have shown that it has specific features, a better prognosis, and increased overall survival. In this review, we summarize some of the most frequent aspects of EBVaGC, including the specific features of this GC subtype, data regarding the potential steps of EBVaGC carcinogenesis, and perspectives on treatment opportunities.

scholarly journals Overview of Epstein–Barr-Virus-Associated Gastric Cancer Correlated with Prognostic Classification and Development of Therapeutic Options

2020 ◽  
Vol 21 (24) ◽  
pp. 9400
Author(s):  
Valli De Re ◽  
Giulia Brisotto ◽  
Ombretta Repetto ◽  
Mariangela De Zorzi ◽  
Laura Caggiari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Response ◽  
Epstein Barr Virus ◽  
The Cancer Genome Atlas ◽  
Barr Virus ◽  
Ebv Infection ◽  
Tumor Environment ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Molecular Phenotypes

Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differences in GC and have led to the identification of an Epstein–Barr virus (EBV)-related GC subtype (EBVaGC), providing new indications for tailored treatment and prognostic factors. This article provides a review of the features of EBVaGC and an update on the latest insights from EBV-related research with a particular focus on the strict interaction between EBV infection and the gastric tumor environment, including the host immune response. This information may help increase our knowledge of EBVaGC pathogenesis and the mechanisms that sustain the immune response of patients since this mechanism has been demonstrated to offer a survival advantage in a proportion of patients with GC.

Aberrantly methylated-differentially expressed genes and pathways in Epstein–Barr virus-associated gastric cancer

2020 ◽  
Vol 16 (6) ◽  
pp. 187-197
Author(s):  
Jing-jing Jing ◽  
Hao Li ◽  
Ze-yang Wang ◽  
Heng Zhou ◽  
Li-ping Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Differentially Expressed Genes ◽  
Epstein Barr Virus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Genome Atlas

Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein–Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.

scholarly journals Efficacy of Immune Checkpoint Inhibitors in Metastatic Epstein-Barr Virus Associated Gastric Cancer (EBVaGC): A Case Series and Review of Literature

2021 ◽  
Author(s):  
Shimeng Liang ◽  
Weibing Leng ◽  
Dan Jiang ◽  
Ming Liu ◽  
Dan Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Epstein Barr Virus ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Metastatic Gastric Cancer ◽  
Pooled Analysis ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background Immunotherapy has revolutionized the treatment of malignant tumors. However, limited clinical data are available to report the efficacy of immune checkpoint inhibitors (ICIs) on Epstein-Barr virus-associated gastric carcinoma. Methods In this study, we report a case series of five patients with metastatic Epstein-Barr virus-associated gastric carcinoma who were treated with ICIs and to perform a pooled analysis of published cases to investigate the efficacy of ICIs in Epstein-Barr virus-associated gastric carcinoma patients. Results Between 2018 and 2020, five metastatic gastric cancer patients with EBV positivity who received PD-1 antibodies treatment were included in the analysis at the authors’ institution. Furthermore, we performed a pooled analysis of the contemporary literature. In our case series, two patients experienced partial response (PR); one patient achieved complete response (CR), whereas two patients had progression disease (PD), resulting an ORR of 60%. In the pooled analysis of all 36 patients, ORR was 48.6% (17/35). For the first line and later lines, it was 75% (3/4) and 45.2% (14/31) respectively. The ORR was 46.7% (14/30) for ICIs monotherapy and improved to 60% (3/5) by combination with chemotherapy. Conclusions These results demonstrated that an EBV-positive status was a reliable biomarker for immunotherapy in metastatic gastric cancer, especially for monotherapy. Immunotherapy combined with chemotherapy may be a better strategy, warranting further large-scale clinical trials for validation.

scholarly journals Establishment of a Screening Method for Epstein-Barr Virus-Associated Gastric Carcinoma by Droplet Digital PCR

2019 ◽  
Vol 7 (12) ◽  
pp. 628 ◽  
Author(s):  
Takuya Shuto ◽  
Jun Nishikawa ◽  
Kanami Shimokuri ◽  
Ayaka Yanagi ◽  
Tatsuya Takagi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Screening Method ◽  
Complete Agreement ◽  
Quantitative Detection ◽  
Serum Samples ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Background: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is classified as one of the molecular subtypes of gastric cancer. We used droplet digital polymerase chain reaction (ddPCR) to enable highly sensitive and quantitative detection of EBV. Methods: EBV-DNA load was calculated based on the copy number of the BamH1-W fragment of EBV by ddPCR, and the cut-off value of EBV-DNA load was set. We conducted both ddPCR and EBER1 ISH to examine whether their results coincided in 158 gastric cancer specimens of unknown EBV status. We prepared 26 biopsy specimens and 49 serum samples including EBVaGC and assayed them by ddPCR. Results: The median values of EBV-DNA load for EBVaGC and EBV-negative control were 17.0 and 0.00308, respectively. A cut-off value of 0.032 was determined for which the sensitivity was 1. Among the 158 gastric cancer specimens, 14 lesions were judged as EBV-positive by the 0.032 cut-off value determined by ddPCR. The results of ddPCR and EBER1 ISH were in complete agreement. Even when using a biopsy specimen as a sample for ddPCR, the EBV-DNA load of all EBVaGCs was larger than the cut-off value. Conclusions: We established a new method of diagnosing EBVaGC from tissue samples by ddPCR.

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