DNA methylation epigenotype expanding to non-polycomb target genes, induced by Epstein-Barr virus infection in human gastric cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE31789 | GEO | 2012/01/04
SECONDARY ACCESSION(S): PRJNA145257
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE31787: Aberrant DNA methylation epigenotype expanding to non-polycomb target genes, induced by Epstein-Barr virus infection in human gastric cancer [Affymetrix Expression] GSE31788: Aberrant DNA methylation epigenotype expanding to non-polycomb target genes, induced by Epstein-Barr virus infection in human gastric cancer [Illumina Methylation] Refer to individual Series
2012-01-04 | E-GEOD-31789 | biostudies-arrayexpress
Project description:Aberrant promoter methylation is known to be deeply involved in human gastric carcinogenesis, while association of Epstein-Barr virus (EBV) to the aberrant methylation has not been fully clarified. We analyzed promoter methylation in clinical gastric cancer cases using illumina's Infinium beadarray, and hierarchical clustering analysis classified gastric cancer into three subgroups: low and high methylation epigenotypes in EBV-negative cases, and markedly higher methylation epigenotype that was completely matched to EBV-positive cases. Three epigenotypes were characterized by three groups of genes: genes methylated specifically in the EBV-positive epigenotype (EBV(+)-markers, e.g. CXXC4, TIMP2, PLXND1), genes methylated both in EBV-positive and high epigenotypes (High-markers, e.g. COL9A2, EYA1, ZNF365), and genes methylated all in EBV-positive, high and low epigenotypes of gastric cancer (Common-markers, e.g. AMPH, SORCS3, AJAP1). Polycomb repressive complex (PRC)-target genes in ES cells were significantly enriched in High- and Common-markers (P=2x10-15 and 2x10-34, respectively), but not in EBV(+)-markers (P=0.2), suggesting a different cause for EBV(+)-marker methylation. Recombinant EBV was infected to low epigenotype gastric cancer cell, MKN7. In all the three independently established clones, DNA methylation was induced in High- and EBV(+)-markers after 18 weeks, demonstrating that EBV-positive epigenotype should involve methylation of Common-, High-, and EBV(+)-markers simultaneously. The de novo methylated genes were overlapped well among the three clones, and the methylation caused gene repression. In summary, gastric cancer was classified into three DNA methylation epigenotypes, EBV-positive gastric cancer showed markedly high methylation epigenotype expanding to non-PRC target genes, and EBV infection per se could induce the EBV-positive epigenotype.
2012-01-04 | GSE31788 | GEO
Project description:Aberrant promoter methylation is known to be deeply involved in human gastric carcinogenesis, while association of Epstein-Barr virus (EBV) to the aberrant methylation has not been fully clarified. We analyzed promoter methylation in clinical gastric cancer cases using illumina's Infinium beadarray, and hierarchical clustering analysis classified gastric cancer into three subgroups: low and high methylation epigenotypes in EBV-negative cases, and markedly higher methylation epigenotype that was completely matched to EBV-positive cases. Three epigenotypes were characterized by three groups of genes: genes methylated specifically in the EBV-positive epigenotype (EBV(+)-markers, e.g. CXXC4, TIMP2, PLXND1), genes methylated both in EBV-positive and high epigenotypes (High-markers, e.g. COL9A2, EYA1, ZNF365), and genes methylated all in EBV-positive, high and low epigenotypes of gastric cancer (Common-markers, e.g. AMPH, SORCS3, AJAP1). Polycomb repressive complex (PRC)-target genes in ES cells were significantly enriched in High- and Common-markers (P=2x10-15 and 2x10-34, respectively), but not in EBV(+)-markers (P=0.2), suggesting a different cause for EBV(+)-marker methylation. Recombinant EBV was infected to low epigenotype gastric cancer cell, MKN7. In all the three independently established clones, DNA methylation was induced in High- and EBV(+)-markers after 18 weeks, demonstrating that EBV-positive epigenotype should involve methylation of Common-, High-, and EBV(+)-markers simultaneously. The de novo methylated genes were overlapped well among the three clones, and the methylation caused gene repression. In summary, gastric cancer was classified into three DNA methylation epigenotypes, EBV-positive gastric cancer showed markedly high methylation epigenotype expanding to non-PRC target genes, and EBV infection per se could induce the EBV-positive epigenotype.
2012-01-04 | GSE31787 | GEO
Project description:DNA methylation epigenotype expanding to non-polycomb target genes, induced by Epstein-Barr virus infection in human gastric cancer
| PRJNA145257 | ENA
Project description:The KT tumor is a transplantable strain of a human Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), established in severe combined immunodeficiency (SCID) mice, with which the cytokine expression of EBVaGC can be investigated without interference from the infiltrating lymphocytes. As a part of a high-density oligonucleotide array (GeneChip) analysis of EBVaGC, the interleukin-1beta (IL-1beta) gene was the only cytokine gene that showed markedly higher expression in the KT tumor cells than in two tumor strains of EBV-negative GC. The results were confirmed by Northern blotting, Western blotting, and enzyme-linked immunosorbent assay. Furthermore, we demonstrated a positive signal for IL-1beta mRNA in the carcinoma cells of a surgically resected EBVaGC, but not in EBV-negative GC, by in situ hybridization. In vitro, IL-1beta increased the cell growth of a GC cell line, TMK1. Thus, IL-1beta may act as an autocrine growth factor in EBVaGC.
| S-EPMC136266 | biostudies-literature
Project description:Epstein-Barr virus associated gastric cancer (EBVaGC) comprises approximately 10% of gastric carcinomas. Multiple factors contribute to tumorigenesis, including EBV driven hypermethylation of tumor suppressor genes, inflammatory changes in gastric mucosa, host immune evasion by EBV and changes in cell cycle pathways. The unique molecular characteristics of EBVaGC, such as programmed death ligand 1 (PD-L1) overexpression, highlight the potential for using EBV as a biomarker for response to immunotherapy. Few studies have reported benefit from immunotherapy in EBV positive cancers, and clinical trials investigating the impact of checkpoint inhibitors in EBVaGC are currently underway. This review provides the most recent updates on molecular pathophysiology, epidemiology, clinical features and treatment advances pertaining to EBVaGC.
| S-EPMC5964025 | biostudies-literature
Project description:Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.
| S-EPMC3917444 | biostudies-literature
Project description:Antibodies directed against the autoantigen p26 were detected in sera from 32 patients with acute Epstein-Barr virus (EBV) infection and clinical symptoms of infectious mononucleosis. P26 has now been identified as the enzyme manganese superoxide dismutase (MnSOD) by comparison of the NH2-terminal amino acid sequence. Antibodies against MnSOD belong to the immunoglobulin class M. They are not detectable in sera of patients with other herpesvirus infections. In the 32 patients investigated, the rise and fall of the autoantibodies coincides with the clinical symptoms. In vitro, the autoantibodies were shown to inhibit the dismutation of superoxide radicals by blocking MnSOD. As presented in the discussion this effect may contribute to the pathogenesis of acute EBV infection.
| S-EPMC2191756 | biostudies-other
Project description:BackgroundPrevious studies reported that Epstein-Barr virus (EBV) may play a causal role in the pathogenesis of gastric remnant carcinoma (GRC). However, there was still some controversy.MethodsArticles published until July 15, 2020, in PubMed, MEDLINE, Embase and CNKI databases were selected. According to the inclusion criteria, corresponding data of included articles were abstracted and used for statistical analysis.ResultsThirteen papers were finally enrolled, nine of which showed the result that the risk of EBV infection rate in the GRC was higher than conventional gastric carcinoma (OR = 5.22, 95% CI 3.89-7.00). In addition, we found that EBV associated GRC (EBVaGRC) had higher rate of Billroth-II (OR = 3.80, 95% CI 1.90-7.57), carcinoma in anastomotic site (OR = 2.41, 95% CI 1.27-4.56) and diffuse type (Lauren classification) (OR = 1.97, 95% CI 1.04-3.73),while sex, initial diagnosis and lymphocytic infiltration were calculated no statistical difference. By genetic polymorphism analysis, "V-val" subtype of EBNA1 (OR = 21.84, 95% CI 11.92-31.76) and "C" subtype of BamHI-W1/I1 (OR = 7.07, 95% CI 1.47-34.03) were observed to be highly expressed in EBVaGRC.ConclusionEBV infection rate in the GRC was higher. Further analysis showed that Billroth-II, carcinoma in anastomotic site and diffuse type (Lauren classification) were associated to EBVaGRC. Through analysis of EBV genome polymorphisms, we thought that "V-val" subtype of EBNA1 and "C" subtype of BamHI-W1/I1 may become predictor of EBVaGRC.
| S-EPMC7437139 | biostudies-literature
Project description:Previous investigations proposed a link between the Epstein-Barr virus (EBV) and lung cancer (LC), but the results are highly controversial largely due to the insufficient sample size and the inherent limitation of the traditional viral screening methods such as PCR. Unlike PCR, current next-generation sequencing (NGS) utilizes an unbiased method for the global assessment of all exogenous agents within a cancer sample with high sensitivity and specificity. In our current study, we aim to resolve this long-standing controversy by utilizing our unbiased NGS-based informatics approaches in conjunction with traditional molecular methods to investigate the role of EBV in a total of 1127 LC. In situ hybridization analysis of 110 LC and 10 normal lung samples detected EBV transcripts in 3 LC samples. Comprehensive virome analyses of RNA sequencing (RNA-seq) data sets from 1017 LC and 110 paired adjacent normal lung specimens revealed EBV transcripts in three lung squamous cell carcinoma and one lung adenocarcinoma samples. In the sample with the highest EBV coverage, transcripts from the BamHI A region accounted for the majority of EBV reads. Expression of EBNA-1, LMP-1 and LMP-2 was observed. A number of viral circular RNA candidates were also detected. Thus, we for the first time revealed a type II latency-like viral transcriptome in the setting of LC in vivo. The high-level expression of viral BamHI A transcripts in LC suggests a functional role of these transcripts, likely as long non-coding RNA. Analyses of cellular gene expression and stained tissue sections indicated an increased immune cell infiltration in the sample expressing high levels of EBV transcripts compared to samples expressing low EBV transcripts. Increased level of immune checkpoint blockade factors was also detected in the sample with higher levels of EBV transcripts, indicating an induced immune tolerance. Lastly, inhibition of immune pathways and activation of oncogenic pathways were detected in the sample with high EBV transcripts compared to the EBV-low LC indicating the direct regulation of cancer pathways by EBV. Taken together, our data support the notion that EBV likely plays a pathological role in a subset of LC.
| S-EPMC6627930 | biostudies-literature