Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity; implications for possible immune adjuvant therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45453 | GEO | 2013/06/23
SECONDARY ACCESSION(S): PRJNA194069
REPOSITORIES: GEO
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. Examination of a gastric carcinoma cell line naturally infected with EBV, SNU-719 using poly-A and ribodepletion RNA-seq data sets
2013-06-23 | E-GEOD-45453 | biostudies-arrayexpress
Project description:Epstein-Barr virus (EBV) is associated with roughly 10% of gastric carcinomas worldwide (EBVaGC). Although previous investigations provide a strong link between EBV and gastric carcinomas, these studies were performed using selected EBV gene probes. Using a cohort of gastric carcinoma RNA-seq data sets from The Cancer Genome Atlas (TCGA), we performed a quantitative and global assessment of EBV gene expression in gastric carcinomas and assessed EBV associated cellular pathway alterations. EBV transcripts were detected in 17% of samples but these samples varied significantly in EBV coverage depth. In four samples with the highest EBV coverage (hiEBVaGC - high EBV associated gastric carcinoma), transcripts from the BamHI A region comprised the majority of EBV reads. Expression of LMP2, and to a lesser extent, LMP1 were also observed as was evidence of abortive lytic replication. Analysis of cellular gene expression indicated significant immune cell infiltration and a predominant IFNG response in samples expressing high levels of EBV transcripts relative to samples expressing low or no EBV transcripts. Despite the apparent immune cell infiltration, high levels of the cytotoxic T-cell (CTL) and natural killer (NK) cell inhibitor, IDO1, was observed in the hiEBVaGCs samples suggesting an active tolerance inducing pathway in this subgroup. These results were confirmed in a separate cohort of 21 Vietnamese gastric carcinoma samples using qRT-PCR and on tissue samples using in situ hybridization and immunohistochemistry. Lastly, a panel of tumor suppressors and candidate oncogenes were expressed at lower levels in hiEBVaGC versus EBV-low and EBV-negative gastric cancers suggesting the direct regulation of tumor pathways by EBV.
| S-EPMC3649992 | biostudies-literature
Project description:To understand epigenic dysregulation of host and viral genes upon EBV infection in human gastric cancer, genome wide transcripts by RNAseq were undertaken for total RNAs of 3 EBVnGC, their isogenic cell lines converted by in vitro EBV-infection and 3 EBV-naturally infected GC cell lines.
2014-09-01 | GSE60873 | GEO
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:Comprehensive gene expression profiles of Epstein-Barr virus (EBV)-associated B cell neoplasm (clinical samples + cell lines)
2014-04-11 | E-MTAB-973 | biostudies-arrayexpress
Project description:The better prognosis of patients with Epstein-Barr virus-positive gastric carcinoma than those with EBV-negative GC is correlated with the degree of recruitment of inflammatory tumor infiltrating cells (TIL) to the vicinity of tumor cells. We hypothesized that the better prognosis would associate with less genetic or epigenetic alterations in EBV(+)GC, or EBV infection should deregulate immune modulator proteins, of which secretion recruit TIL. Therefore we performed mRNA expression profilings in EBV(-)GC and EBV(+)GC, each of which was pair wise compared with their normal control. We found that EBV(+)GC had much more molecular homogeneity with focused alterations in immune modulator genes; The Pearson correlation matrix analyses demonstrated that EBV(+)GC tumor showed remarkably high tumor homogeneity. While EBV(-)GC had considerable number genes that are differentially expressed genes from their normal counterparts, EBV(+)GC showed only a handful, almost 20 fold less number of DEG than EBV(-)GC under the same p value cutoff (p<0.001). Gene ontology and pathway analyses showed that while pathways of cation homeostasis, digestion and ion transport were commonly deregulated in both GC types, genes for chromatin assembly, prostaglandin receptor activity, pattern specification process are selectively deregulated in EBV(-)GC tumors. In contrast, pathways or genes for cytokine activity, immune response and lipoprotein particle clearance are selectively deregulated in EBV(+)GC tumors. These results demonstrate that EBV(+)GC inherently evolves to high homogeneity with fewer changes in gene expression and these secret immune modulatory chemokines could recruit reactive immune cells to EBV(+)GC, leading to favorable microenvironment for cancer suppression.
2014-03-01 | GSE51575 | GEO
Project description:The better prognosis of patients with Epstein-Barr virus-positive gastric carcinoma than those with EBV-negative GC is correlated with the degree of recruitment of inflammatory tumor infiltrating cells (TIL) to the vicinity of tumor cells. We hypothesized that the better prognosis would associate with less genetic or epigenetic alterations in EBV(+)GC, or EBV infection should deregulate immune modulator proteins, of which secretion recruit TIL. Therefore we performed mRNA expression profilings in EBV(-)GC and EBV(+)GC, each of which was pair wise compared with their normal control. We found that EBV(+)GC had much more molecular homogeneity with focused alterations in immune modulator genes; The Pearson correlation matrix analyses demonstrated that EBV(+)GC tumor showed remarkably high tumor homogeneity. While EBV(-)GC had considerable number genes that are differentially expressed genes from their normal counterparts, EBV(+)GC showed only a handful, almost 20 fold less number of DEG than EBV(-)GC under the same p value cutoff (p<0.001). Gene ontology and pathway analyses showed that while pathways of cation homeostasis, digestion and ion transport were commonly deregulated in both GC types, genes for chromatin assembly, prostaglandin receptor activity, pattern specification process are selectively deregulated in EBV(-)GC tumors. In contrast, pathways or genes for cytokine activity, immune response and lipoprotein particle clearance are selectively deregulated in EBV(+)GC tumors. These results demonstrate that EBV(+)GC inherently evolves to high homogeneity with fewer changes in gene expression and these secret immune modulatory chemokines could recruit reactive immune cells to EBV(+)GC, leading to favorable microenvironment for cancer suppression. All patients underwent the surgery for advanced gastric carcinoma (GC) except one patient with early GC. The EBV-presence in the GC was verified by in situ EBV-encoded small RNA (ERER) staining.. The 14 paired EBV(-)GC patients and 12 paired EBV(+)GC patients were selected for this study. Tumor tissue (T)and normal tissues (N) from distant sites from tumor areas were dissected, frozen at -80C and were subjected to RNA purification, mRNA array profiling analyses.
2014-03-01 | E-GEOD-51575 | biostudies-arrayexpress
Project description:Reactive oxygen species (ROS) mediated oxidative stress plays an increasingly extensive role in tumorigenesis. Oxidative stress is also an important mechanism for host cells to resist infection by pathogenic microorganisms. Viruses have a similar defense mechanism. Studies have shown that ROS levels are elevated during in vitro and in vivo EBV infection. In nasopharyngeal carcinoma, EBV latent membrane protein LMP1 "REDOX" nasopharyngeal carcinoma cells by up-regulating NRF2 and NOX2, acquiring new REDOX homeostasis to tolerate higher levels of ROS. In gastric cancer, EBV upregulates NOX2 by down-regulating miR34a via EBNA1, thereby enhancing the antioxidant capacity of host cells. In addition, oxidative stress is involved in the lytic reactivation of EBV, but the specific mechanism is not clear. GPX4 is an important ROS scavenger that plays a role in maintaining cellular REDOX homeostasis. Our study showed that GPX4 is relatively highly expressed in EBV-positive gastric cancer cell lines, which can promote tumor proliferation and migration, and we found that GPX4 helps maintain latent infection of EBV in gastric cancer. In order to further explore the specific mechanism, we performed transcriptome sequencing analysis after knocking down GPX4 expression in AGS-EBV cells.
2025-01-16 | GSE286972 | GEO
Project description:Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt’s lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7), but the precise role of USP7 in controlling EBNA1 stability and function is not fully understood. Here, we show that pharmacological inhibitors and small interfering RNA (siRNA) targeting USP7 reduce EBNA1 protein levels. The USP7 inhibitor GNE6776 altered EBNA1 protein interactions, including disrupting its ability to bind to USP7. GNE6776 also inhibited EBNA1 binding to EBV oriP DNA and reduced viral episome copy number. GNE6776 selectively inhibited EBV+ gastric and lymphoid cell proliferation in cell culture and slowed EBV+ tumor growth in mouse xenograft models. Transcriptomic studies revealed that USP7 inhibition differentially affected EBV+ cancer cells compared to EBV- cells with a significant effect on chromosome segregation and mitotic cell division pathways. Our findings indicate that USP7 inhibition perturbs EBNA1 stability and function and can be exploited to target EBV+ cancer cells selectively.
2025-01-31 | GSE284839 | 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