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

Re, Vallì De; Brisotto, Giulia; Repetto, Ombretta; Zorzi, Mariangela De; Caggiari, Laura; Zanussi, Stefania; Alessandrini, Lara; Canzonieri, Vincenzo; Miolo, Gianmaria; Puglisi, Fabio; Belluco, Claudio; Steffan, Agostino; Cannizzaro, Renato

doi:10.3390/ijms21249400

Cited by 15 publications

(10 citation statements)

References 177 publications

(210 reference statements)

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“…Additionally, Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) are the main risk factors for GC development [1,2]. Nevertheless, the distribution of histological subtypes of GC and the frequencies of H. pylori-and EBV-related GC vary worldwide [4][5][6]. The genetic diffuse GC accounts for approximately 1-3% of GC cases [7].…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Genes Reveals BGN Predicting Overall Survival and Tumor Immune Infiltration of Gastric Cancer

Chen¹,

Yang²

2021

Computational and Mathematical Methods in Medicine

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Gastric cancer (GC) is one of the most widely occurring malignancies worldwide. Although the diagnosis and treatment strategies of GC have been greatly improved in the past few decades, the morbidity and lethality rates of GC are still rising due to lacking early diagnosis strategies and powerful treatments. In this study, a total of 37 differentially expressed genes were identified in GC by analyzing TCGA, GSE118897, GSE19826, and GSE54129. Using the PPI database, we identified 17 hub genes in GC. By analyzing the expression of hub genes and OS, MFAP2, BGN, and TREM1 were related to the prognosis of GC. In addition, our results showed that higher levels of BGN exhibited a significant correlation with shorter OS time in GC. Nomogram analysis showed that the dysregulation of BGN could predict the prognosis of GC. Moreover, we revealed that BGN had a markedly negative correlation with B cells but had positive correlations with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC samples. The pan-cancer analysis demonstrated that BGN was differentially expressed and related to tumor-infiltrating immune cells across human cancers. This study for the first time comprehensively revealed that BGN was a potential biomarker for the prediction of GC prognosis and tumor immune infiltration.

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Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Genes Reveals BGN Predicting Overall Survival and Tumor Immune Infiltration of Gastric Cancer

Chen¹,

Yang²

2021

Computational and Mathematical Methods in Medicine

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“…Epstein–Barr virus represents the most thoroughly researched gamma‐herpes virus, as well as the prototypical lymphocryptoviral 54 . The first virus to be proven to cause cancer in humans is EBV, a double‐stranded DNA virus from the herpesvirus family 55 . Multiple investigations and systematic analyses have demonstrated that having a history of infectious mononucleosis (IM) substantially raises the possibility of developing MS and that people who are EBV seropositive are more likely to develop MS, especially if they have antibodies against the EBV Nuclear Antigen 1 (EBNA‐1) and Viral Capsid Antigen proteins 56 .…”

Section: Discussionmentioning

confidence: 99%

The association between various viral infections and multiple sclerosis: An umbrella review on systematic review and meta‐analysis

Bakhshi,

Eslami,

Norouzi

et al. 2023

Reviews in Medical Virology

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Multiple Sclerosis (MS) is one of the immune‐mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the pathogenesis of MS. Also, it can be said that infections are a key component of the host's response to MS development. Finally, we evaluated the relationship between different pathogens and MS disease in this umbrella research. We systematically collected and analysed multiple meta‐analyses focused on one particular topic. We utilised the Scopus, PubMed, and Web of Science databases starting with inception until 30 May 2023. The methodological quality of the analysed meta‐analysis has been determined based on Assessing the Methodological Quality of Systematic Reviews 2 and Grade, and graph construction and statistical analysis were conducted using Comprehensive Meta‐Analysis. The Confidence Interval of effect size was 95% in meta‐analyses, and p < 0.05 indicated a statistically meaningful relationship. The included studies evaluated the association between MS and 12 viruses containing SARS‐CoV‐2, Epstein–Barr virus (EBV), Hepatitis B virus, varicella–zoster virus (VZV), human herpesvirus 6 (HHV‐6), HHV‐7, HHV‐8, HSV‐1, HSV‐2, Cytomegalovirus, Human Papillomavirus, and influenza. SARS‐CoV‐2, with a 3.74 odds ratio, has a significantly more potent negative effect on MS among viral infections. After that, EBV, HHV‐6, HSV‐2, and VZV, respectively, with 3.33, 2.81, 1.76, and 1.72 odds ratios, had a significantly negative relationship with MS (p < 0.05). Although the theoretical evidence mostly indicates that EBV has the greatest effect on MS, recent epidemiological studies have challenged this conclusion and put forward possibilities that SARS‐CoV‐2 is the culprit. Hence, it was necessary to investigate the effects of SARS‐CoV‐2 and EBV on MS.

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“…EBVaGCs are reported to be correlated with lower T and N stages, outlining a better prognosis than the EBER-ISH negative cases, especially during the early stage in the submucosa [38]. However, these findings are contradicted by other papers which highlight no differences in survival between EBVaGC and EBV-negative gastric carcinoma (EBVnGC) cases after surgery and/or conventional chemotherapy [39]. In our series, Kaplan-Meier curves showed that EBER-ISH positive cases have significantly better overall survival (OS) than EBER-ISH negative cases.…”

Section: Survival Analysismentioning

confidence: 91%

EBV persistence in gastric cancer cases conventionally classified as EBER-ISH negative

Siciliano

Tornambè

Cevenini

et al. 2022

Infect Agents Cancer

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Background The Epstein-Barr virus (EBV) causes various B-cell lymphomas and epithelial malignancies, including gastric cancer (GC) at frequencies ranging from 5 to 10% in adenocarcinomas (ADK) to 80% in GC with lymphoid stroma (GCLS). Using high-sensitivity methods, we recently detected EBV traces in a large cohort of EBV-negative B-cell lymphomas, suggesting a hit-and-run mechanism. Methods Here, we used routine and higher-sensitivity methods [droplet digital PCR (ddPCR) for EBV segments on microdissected tumour cells and RNAscope for EBNA1 mRNA] to assess EBV infection in a cohort of 40 GCs (28 ADK and 12 GCLS). Results ddPCR documented the presence of EBV nucleic acids in rare tumour cells of several cases conventionally classified as EBV-negative (ADK, 8/26; GCLS, 6/7). Similarly, RNAscope confirmed EBNA1 expression in rare tumour cells (ADK, 4/26; GCLS, 3/7). Finally, since EBV induces epigenetic changes that are heritable and retained after complete loss of the virus from the host cell, we studied the methylation pattern of EBV-specifically methylated genes (Timp2, Eya1) as a mark of previous EBV infection. Cases with EBV traces showed a considerable level of methylation in Timp2 and Eya1 genes that was similar to that observed in EBER-ISH positive cases and greater than cases not featuring any EBV traces. Conclusions These findings suggest that: (a) EBV may contribute to gastric pathogenesis more widely than currently acknowledged and (b) indicate the methylation changes as a mechanistic framework for how EBV can act in a hit-and-run manner. Finally, we found that the viral state was of prognostic significance in univariate and multivariate analyses.

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

Cited by 15 publications

References 177 publications

Identification of Differentially Expressed Genes Reveals BGN Predicting Overall Survival and Tumor Immune Infiltration of Gastric Cancer

Identification of Differentially Expressed Genes Reveals BGN Predicting Overall Survival and Tumor Immune Infiltration of Gastric Cancer

The association between various viral infections and multiple sclerosis: An umbrella review on systematic review and meta‐analysis

EBV persistence in gastric cancer cases conventionally classified as EBER-ISH negative

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