Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity; implications for possible immune adjuvant therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Erik Flemington
PROVIDER: E-GEOD-45453 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Our goal of this study was to perform quantitative and global assessment of EBV gene expression in gastric carcinomas and assess EBV associated cellular pathway alterations.
2013-06-23 | GSE45453 | GEO
Project description:We investigate the expression of miRNA in exosome of EBV-positive gastric carcinoma cells. The exosomes of EBV-positive and negative gastric carcinoma cells were separated by ultracentrifugation, the morphology of exosomes was identified by transmission electron microscopy, the exosome size was analyzed by Nanosight, and the expression of exosome membrane protein CD63 and CD81 was detected by western blot. High-throughput sequencing was used to detect miRNA expression profiles in gastric cancer cell lines and their exosomes. Under the ultra-microscopic electron microscope, the exosomes are seen as a typical translucent cup-like structure or a flat spherical structure. The nanoparticle tracking analyzer (Nanosight) showed that the exosomes were between 30 and 150 nm in diameter. Western blot(WB) assays showed that exosomes secreted by EBVaGC and EBVnGC cells expressed specific exosome membrane-associated proteins CD63 and CD81. High-throughput sequencing revealed that EBVaGC(SNU-719) and EBVnGC(AGS) and their secreted exosomes were highly expressed with certain human miRNAs, among which AGS-exo was highly expressed with hsa-miR-23b-3p, hsa-miR-320a-3p, and hsa-miR-4521. SNU-719-exo was highly expressed as hsa-miR-21-5p, hsa-miR-148a-3p and hsa-miR-7-5p. Nearly all EBV-related miRNAs (EBV-miRNA) were expressed in SNU-719 cells and their exosomes, among which EBV-miR-BART1-5p, EBV-miR-BART17-3p and EBV-miR-BART18-5p were the highest in SNU-719 cells, EBV-miR-BART1-5p, EBV-miR-BART18-5p and EBV-miR-BART17-3p were the highest in SNU-719-exo.
2022-03-14 | GSE198354 | GEO
Project description:Aim: EBV encode at least 44 miRNAs involved in immune regulation and disease progression. Exosomes can be used as carriers of EBV-miRNA-BART intercellular transmission and affect the biological behavior of cells. We characterized exosomes and established a co-culture experiment of exosomes to explore the mechanism of miR-BART1-3p transmission through the exosome pathway and its influence on tumor cell proliferation and invasion. Materials and methods: Exosomes of EBV-positive and EBV-negative gastric cancer cells were characterized by transmission electron microscopy, Nanosight and western blotting, and miRNA expression profiles in exosomes were sequenced with high throughput. Exosomes with high or low expression of miR-BART1-3p were co-cultured with AGS cells to study the effects on proliferation, invasion and migration of gastric cancer cells. The target genes of EBV-miR-BART1-3p were screened and predicted by PITA, miRanda, RNAhybrid, virBase and Diana-Tarbase v.8 databases, and the expression of the target genes after co-culture was detected by qPCR. Results：The exosomes secreted by EBV positive and negative gastric cancer cells range in diameter from 30 nm to 150nm and express the exosomal signature proteins CD63 and CD81. High throughput sequencing showed that exosomes expressed some human miRNAs, among which has-miR-23b-3p, has-miR-320a-3p and has-miR-4521 were highly expressed in AGS-exo. has-miR-21-5p, has-miR-148a-3p and has-miR-7-5p were highly expressed in SNU-719-exo. All EBV miRNAs were expressed in SNU-719 cells and their exosomes, among which EBV- miR-Bart1-5p, EBV- miR-bart22 and EBV- miR-bart16 were the highest in SNU-719 cells. EBV-miR-BART1-5p, EBV-miR-BART10-3p and EBV-miR-BART16 were the highest in SNU-719-exo. After miR-BART1-3p silencing in gastric cancer cells, the proliferation, healing, migration and invasion of tumor cells were significantly improved. Laser confocal microscopy showed that exosomes could carry miRNA into recipient cells. After co-culture with miR-BART1-3p silenced exosomes, the proliferation, healing, migration and invasion of gastric cancer cells were significantly improved. The target gene of miR-BART1-3p was FMA168A, MACC1, CPEB3, ANKRD28 and USP37 after screening by targeted database. CPEB3 was not expressed in all exosome co-cultured cells, while ANKRD28, USP37, MACC1 and FAM168A were all expressed to varying degrees. USP37 and MACC1 are down-regulated after up-regulation of miR-BART1-3p, which may be the key target genes for miR-BART1-3p to regulate the proliferation of gastric cancer cells through exosomes. Conclusions: miR-BART1-3p can affect the growth of tumor cells through exosome pathway. The proliferation, healing, migration and invasion of gastric cancer cells were significantly improved after co-culture with exosomes of miR-BART1-3p silenced expression. USP37 and MACC1 may be potential target genes of miR-BART1-3p in regulating cell proliferation.
2023-03-13 | GSE227017 | GEO
Project description: Not available
| S-EPMC3649992 | biostudies-literature
Project description:Gastric cancer is one of the most common cancers worldwide. Epstein-Barr virus-associated gastric cancer accounts for approximately 10% of all gastric cancers. EBV expresses its own proteins and miRNAs (BART miRNAs) and regulates host gene expression. In this study, we examined the effect of EBV infection on host mRNA expression. Differential gene expression was analyzed between EBV-negative human gastric cancer cell line AGS and EBV-positive human gastric cancer cell line AGS-EBV.
2019-10-14 | GSE135644 | GEO
Project description:Time-series comprehensive DNA methylation analysis after EBV infection in the immortalised normal gastric epithelial cell line, GES1, and low methylation gastric cancer cell line, MKN7. Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across 485,577 CpG sites. Samples included 9 GES1 with and without EBV infection, 5 MKN7 with and without EBV infection, EBV+ gastric cancer cell and xenograft, SNU719 and KT, 2 normal gastric mucosae, 2 low-methylation gastric cancer cases, and 2 high-methylation gastric cancer cases.
2017-04-28 | GSE89269 | 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 | 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:Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma cells. In accordance with these observations, CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, respectively. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitor BAY 11-7082. Furthermore, EBV encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 over-expression. Finally, CXCL8 is positively correlated with overall survival in gastric carcinoma patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in gastric carcinoma via NF-κB signaling and CXCL8 may serve as a novel anti-tumor target for EBVaGC.
2021-10-14 | GSE185627 | GEO
Project description:Extensive DNA methylation in promoter regions is observed in gastric cancer with Epstein-barr virus (EBV) infection and EBV infection is the cause to induce this extensive hypermethylaiton phenotype in gastric epithelial cells. From transcriptome analysis, we found that TET2, one of the demethylase enzymes, was downregulated by EBV infection in gastric epithelial cell line MKN7. TET2 was overexpressed in a gastric epithelial cell line, GES1, to see its function and the hydroxymethylation, a byproduct of DNA demethylation, acquired genes by TET2 overexpression and methylation acquired genes by EBV infection were significantly overlapped. These suggested that hydroxymethylation by TET2 could function to keep unmethylated status of genes before EBV infection, and TET2 depression could contribute to methylation acquisition of these target genes after EBV infection.
2017-04-28 | GSE84897 | GEO