Clinicopathological characteristics of Epstein-Barr virus-positive gastric cancer in Latvia

Gasenko, Evita; Isajevs, Sergejs; Camargo, M. Constanza; Offerhaus, G. Johan A.; Poļaka, Inese; Gulley, Margaret L.; Škapars, Roberts; Sīviņš, Armands; Kojalo, Ilona; Kirshners, Arnis; Šantare, Daiga; Pavlova, Jelizaveta; Sjomina, Olga; Liepina, E.; Tzivian, Lilian; Rabkin, Charles S.; Leja, Mārcis

doi:10.1097/meg.0000000000001521

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…There was approximately average 10% EBV positive cases in GC samples worldwide (35,36). For Latvia GC population, EBV positivity was a favorable prognostic factor in GC while it had no significant difference in other relative large cohort (37). Not only the intrinsic alterations of MSI and EBV infected cells but also the tumor microenvironment (TME) contributes to these clinical characteristics to some extent.…”

Section: Discussionmentioning

confidence: 99%

The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer

et al. 2020

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Background: Gastric cancer (GC) is the third leading fatal cancer in the world and its incidence ranked second among all malignant tumors in China. The molecular classification of GC, proposed by the The Cancer Genome Atlas (TCGA), was added to the updated edition (2019) of WHO classification for digestive system tumor. Although MSI and EBV subtypes appeared as ever-increasingly significant roles in immune checkpoint inhibitor therapy, the underlying mechanisms are still unclear. Methods: We systematically summarized the relationship between EBV, d-MMR/MSI-H subtypes and clinicopathological parameters in 271 GC cases. Furthermore, GSE62254/ACRG and TCGA-STAD datasets, originated from Gene Expression Omnibus (GEO) and TCGA respectively, were analyzed to figure out the prognosis related molecular characteristics by bioinformatics methods. Results: Patients with MSI subtype had better prognosis than the MSS subtype (P = 0.013) and considered as an independent biomarker by the univariate analysis (P = 0.017) and multivariate analysis (P = 0.050). While there was no significant difference between EBV positive and negative tissues (P = 0.533). The positive prognostic value conferred by MSI in different cohorts was revalidated via the clinical analysis of GSE62254/ACRG and TCGA-STAD datasets regardless of race. Then key gene module that tightly associated with better status and longer OS time for MSI cases was obtained from weighted gene co-expression network analysis(WGCNA). NUBP2 and ENDOG were screened from the gene cluster and oxidative phosphorylation, reactive oxygen species(ROS) and glutathione metabolism were analyzed to be the differential pathways in their highly expressed groups. Conclusions: Our results manifested the significant prognostic value of MSI in Chinese GC cohort and comparisons with other populations. More opportunities to induce apoptosis of cancer cells, led by the unbalance between antioxidant system and ROS accumulation, lay foundations for unveiling the better prognosis in MSI phenotype through the bioinformatics analysis.

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Section: Discussionmentioning

confidence: 99%

The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer

et al. 2020

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“…In the present study, the estimated EBV positive rate was 11.3%. EBV positive rates ranged from 1.2% to 89.2% in the individual eligible studies [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

2020

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Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein–Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088–0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096–0.194), 0.103 (95% CI: 0.077–0.137), 0.080 (95% CI: 0.061–0.106), and 0.042 (95% CI: 0.016–0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428–0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.

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“…In 2018, Panda et al (13) found EBV-positive gastric cancer with low mutation burden to be a subset of microsatellitestable (MSS) gastric cancer, which may respond to immune checkpoint therapy. Thus, EBVpositive gastric cancer is now considered a unique molecular subtype of gastric cancer (14) and is associated with good prognosis in patients (15). At present, there is no article to summarize and analyze the characteristics, mechanisms, and treatment of EBV-positive gastric cancer, including latency proteins.…”

Section: Introductionmentioning

confidence: 99%

EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives

Sun

Jia

et al. 2020

Front. Oncol.

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Gastric cancer is the fifth most common malignant tumor and second leading cause of cancer-related deaths worldwide. With the improved understanding of gastric cancer, a subset of gastric cancer patients infected with Epstein–Barr virus (EBV) has been identified. EBV-positive gastric cancer is a type of tumor with unique genomic aberrations, significant clinicopathological features, and a good prognosis. After EBV infects the human body, it first enters an incubation period in which the virus integrates its DNA into the host and expresses the latent protein and then affects DNA methylation through miRNA under the action of the latent protein, which leads to the occurrence of EBV-positive gastric cancer. With recent developments in immunotherapy, better treatment of EBV-positive gastric cancer patients appears achievable. Moreover, studies show that treatment with immunotherapy has a high effective rate in patients with EBV-positive gastric cancer. This review summarizes the research status of EBV-positive gastric cancer in recent years and indicates areas for improvement of clinical practice.

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Clinicopathological characteristics of Epstein-Barr virus-positive gastric cancer in Latvia

Cited by 17 publications

References 29 publications

The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer

The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives

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