ASTE1 frameshift mutation triggers the immune response in Epstein-Barr virus-associated gastric cancer

Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR = 3.4; p-trend = 0.004), interleukin (IL)-10 (OR = 2.4; p-trend = 0.019), CCL19 (OR = 2.3; p-trend = 0.019), CCL11 (OR = 2.2; p-trend = 0.026), IL-17A (OR = 2.0; p-trend = 0.038) and CCL8 (OR = 1.9; p-trend = 0.049). Systemic responses to EBV-positive gastric cancer are characterized by alterations in chemokines and PD-L1. Profiling of these molecules may enable non-invasive diagnosis of EBV status when tumor tissue is unavailable. Our findings provide theoretical justification for clinical evaluations of immune checkpoint therapy for EBV-positive gastric cancer.

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Deregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes

Gastroenterology ◽

10.1053/j.gastro.2014.09.020 ◽

2015 ◽

Vol 148 (1) ◽

pp. 137-147.e9 ◽

Cited By ~ 54

Author(s):

Sun Young Kim ◽

Charny Park ◽

Ha-Jung Kim ◽

Jihyun Park ◽

Jinha Hwang ◽

...

Keyword(s):

Gastric Cancer ◽

Immune Response ◽

Epstein Barr Virus ◽

Barr Virus ◽

Immune Response Genes ◽

Epstein Barr

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

International Journal of Molecular Sciences ◽

10.3390/ijms21249400 ◽

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.

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The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer

OncoImmunology ◽

10.1080/2162402x.2021.1938381 ◽

2021 ◽

Vol 10 (1) ◽

pp. 1938381

Author(s):

Xiao-Li Wei ◽

Qian-Wen Liu ◽

Fu-Rong Liu ◽

Sha-Sha Yuan ◽

Xiao-Fen Li ◽

...

Keyword(s):

Gastric Cancer ◽

Predictive Value ◽

Epstein Barr Virus ◽

Programmed Death Ligand 1 ◽

Barr Virus ◽

Programmed Death ◽

Clinicopathological Significance ◽

Epstein Barr

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Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

Nature Communications ◽

10.1038/s41467-021-23356-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jieti Wang ◽

Ruochen Li ◽

Yifan Cao ◽

Yun Gu ◽

Hanji Fang ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

T Cells ◽

Epstein Barr Virus ◽

Effector Memory ◽

Feature Identification ◽

Barr Virus ◽

T Cell Infiltration ◽

Epstein Barr ◽

Gastric Cancer Patients

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.

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Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

Cancer Cell International ◽

10.1186/s12935-021-02077-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zeyang Wang ◽

Zhi Lv ◽

Qian Xu ◽

Liping Sun ◽

Yuan Yuan

Keyword(s):

Gastric Cancer ◽

Functional Analysis ◽

Protein Expression ◽

Epstein Barr Virus ◽

Protein Profile ◽

Expression Patterns ◽

Clinicopathological Parameters ◽

Differential Proteomics ◽

Barr Virus ◽

Epstein Barr

Abstract Background Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed. Methods Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue. Results The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC. Conclusions The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.

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