Abstract 789: Development and validation of a capture based NGS assay that enables the detection of Epstein Barr virus from gastric cancer patients' tumor tissues

Author(s):  
Yajie Hu ◽  
Bo Yang ◽  
Lei Wang ◽  
Shiyi Liu ◽  
Lei Liang ◽  
...  
2020 ◽  
Author(s):  
Ahmad Tavakoli ◽  
Seyed Hamidreza Monavari ◽  
Farid Solaymani Mohammadi ◽  
Seyed Jalal Kiani ◽  
Saber Armat ◽  
...  

Abstract Background: Numerous studies conducted over the past 30 years have pointed to the presence of Epstein–Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer. Methods: A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a random effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies with matched pairs design. Results: The pooled prevalence of EBV in 20411 gastric cancer patients was 8.78% (95% CI: 7.75-9.93%; I 2 =83.0%). The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.85%, vs 5.72%) ( P <0.01). EBV was more prevalent in the cardia (12.47%) and in the body (11.68%) compared to the antrum (6.29%) ( P <0.01). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled OR between EBV infection and gastric cancer risk was 18.56 (95% CI: 15.68–21.97; I 2 = 55.4%). Conclusion: EBV infection is associated with more than 18 times increase risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer.


2020 ◽  
Author(s):  
Ahmad Tavakoli ◽  
Seyed Hamidreza Monavari ◽  
Farid Solaymani Mohammadi ◽  
Seyed Jalal Kiani ◽  
Saber Armat ◽  
...  

Abstract Background: Numerous studies conducted over the past 30 years have pointed to the presence of Epstein–Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer. Methods: A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a random-effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies with matched pairs design. Results: The pooled prevalence of EBV in 20411 gastric cancer patients was 8.78% (95% CI: 7.75-9.93%; I 2 =83.0%). The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.85%, vs. 5.72%) ( P <0.01). EBV was more prevalent in the cardia (12.47%) and the body (11.68%) compared to the antrum (6.29%) ( P <0.01). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled OR between EBV infection and gastric cancer risk was 18.56 (95% CI: 15.68–21.97; I 2 = 55.4%). Conclusions: EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer.


2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Carolina Rosal Teixeira de Souza ◽  
Kátia Soares de Oliveira ◽  
Jefferson José Sodré Ferraz ◽  
Mariana Ferreira Leal ◽  
Danielle Queiroz Calcagno ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jieti Wang ◽  
Ruochen Li ◽  
Yifan Cao ◽  
Yun Gu ◽  
Hanji Fang ◽  
...  

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.


Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1220 ◽  
Author(s):  
Yoon ◽  
Kim ◽  
Long ◽  
Min ◽  
Kim ◽  
...  

The metabolic landscape of Epstein–Barr-virus-associated gastric cancer (EBVaGC) remains to be elucidated. In this study, we used transcriptomics, metabolomics, and lipidomics to comprehensively investigate aberrant metabolism in EBVaGC. Specifically, we conducted gene expression analyses using microarray-based data from gastric adenocarcinoma epithelial cell lines and tissue samples from patients with clinically advanced gastric carcinoma. We also conducted complementary metabolomics and lipidomics using various mass spectrometry platforms. We found a significant downregulation of genes related to metabolic pathways, especially the metabolism of amino acids, lipids, and carbohydrates. The effect of dysregulated metabolic genes was confirmed in a survival analysis of 3951 gastric cancer patients. We found 57 upregulated metabolites and 31 metabolites that were downregulated in EBVaGC compared with EBV-negative gastric cancer. Sixty-nine lipids, mainly ether-linked phospholipids and triacylglycerols, were downregulated, whereas 45 lipids, mainly phospholipids, were upregulated. In total, 15 metabolisms related to polar metabolites and 15 lipid-associated pathways were involved in alteration of metabolites by EBV in gastric cancer. In this work, we have described the metabolic landscape of EBVaGC at the multi-omics level. These findings could help elucidate the mechanism of EBVaGC oncogenesis.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3107
Author(s):  
Caroline de Fátima Aquino Moreira-Nunes ◽  
Cláudia Nazaré de Souza Almeida Titan Martins ◽  
Danielle Feio ◽  
Isamu Komatsu Lima ◽  
Leticia Martins Lamarão ◽  
...  

Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein–Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan–Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15509-e15509
Author(s):  
Raghav Sundar ◽  
Aditi Qamra ◽  
Angie Lay Keng Tan ◽  
Shenli Zhang ◽  
Cedric Chuan Young Ng ◽  
...  

e15509 Background: We recently elicited the role of epigenetic promoter alterations as a mechanism of immune-evasion and primary resistance to immune checkpoint inhibition in gastric cancer. High prevalence of epigenetic modifications are known to occur in Epstein-Barr virus associated gastric cancer (EBVaGC). EBVaGC has high response rates to anti-PD-1 immune checkpoint inhibitors and is associated with high levels of PD-L1 expression. However, not all EBVaGC express PD-L1 and mechanisms that mediate these phenomena are unknown. Methods: We performed NanoString profiling and PD-L1 immunohistochemistry (using Dako PD-L1 IHC 22C3) on tissue from gastric cancer patients undergoing primary tumor resections at Samsung Medical Centre, South Korea. NanoString panel was designed for 90 recurrent somatic alternate promoter-related genes, and immune-related genes including PD-L1. EBV status was determined using EBV-encoded RNA in situ hybridization and categorized as EBVaGC and EBV-negative. Samples in the top-quartile of alternate promoter utilization were classified as APhigh and the remaining APlow. Results: A total of 272 samples (EBVaGC n = 79; EBV-negative n = 193) were included in this study. EBVaGC had significantly higher PD-L1 expression (p < 0.001) compared to EBV-negative samples. APhigh group (n = 67) consisted of 61 EBV-negative and 6 EBVaGC samples. EBVaGC APhigh tumors had significantly lower PD-L1 transcript expression compared to EBVaGC APlow tumors (p = 0.011, Wilcoxon-rank sum). Similar correlation was also found with PD-L1 IHC combined positive score (CPS)(median CPS score 1 vs 8, p = 0.047). There was a trend towards poorer survival for EBVaGC APhigh tumors (vs EBVaGC APlow; HR 0.23, 95% CI: 0.046 – 1.23, p = 0.087). EBV-negative APhigh tumors also had lower PD-L1 expression (vs EBV-negative APlow; p = 0.046, Wilcoxon-rank sum). Conclusions: Increased utilization of epigenetic alternate promoter isoforms correlates with lower transcriptomic and protein expression of PD-L1 in EBVaGC. Here we describe a potential mechanism of immune-evasion to explain low immune-infiltration and PD-L1 expression that occurs in a group of EBVaGC that is traditionally considered highly immunogenic.


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