Genomic Analyses of early-stage diffuse-type gastric cancer lacking Helicobacter pylori infection
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PROVIDER: PRJNA530547 | ENA |
REPOSITORIES: ENA
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Project description:We performed the expression RNA-seq experiments for mRNA of gastric cancer tissue. Most of gastric cancers (GCs) are accompanied by Helicobacter pylori (HP) infection. However, a very limited fraction lacks any signs of HP infection and exhibits early-stage diffuse (ED) phenotype. Although previous genomic cohorts have identified multiple driver mutations for gastric cancers including diffuse-type histology, any driver event of GC without HP has not been elucidated. The present study aims to explore the molecular mechanism with comprehensive genomic and transcriptomic analyses by comparing EDGC with and without HP. EDGCs were classified as HP-negative based on the following criteria: 1) no antibiotic eradication history, 2) no atrophic appearance by endoscopy, 3) no atrophic appearance by histology, 4) negativity in two or more tests such as rapid urease, urease breath, serum antibody, stool antigen and serum pepsinogen tests. DNAs and RNAs were extracted from EDGCs with over 10 mm in diameter to secure sufficient amount of cancer tissues. Laser-capture microdissection was then used to reduce contamination of normal cells for further molecular assays. For transcriptome analyses, we conducted RNA-seq of 2 HP-positive and 4 HP-negative fresh frozen EDGCs obtained endoscopically
2022-03-25 | GSE129219 | GEO
Project description:Helicobacter pylori colonization of the human stomach is a strong risk factor for gastric cancer. To investigate H. pylori-induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in H. pylori-infected animals, and transcriptional profiling revealed a loss of markers for these cell types. We then assessed the spatial distribution and relative abundance of proteins in the gastric tissues using imaging mass spectrometry and liquid chromatography with tandem mass spectrometry (LC-MS/MS). We detected striking differences in protein content of corpus and antrum tissues. 492 proteins were preferentially localized to the corpus in uninfected animals. The abundance of 91 of these proteins was reduced in H. pylori-infected corpus tissues exhibiting atrophic gastritis compared to infected corpus tissues with non-atrophic gastritis or uninfected corpus tissues; these included numerous proteins with metabolic functions. Fifty proteins localized to the corpus in uninfected animals were diffusely delocalized throughout the stomach in infected tissues with atrophic gastritis; these included numerous proteins with roles in protein processing. Corresponding alterations were not detected in animals infected with a H. pylori ∆cagT mutant (lacking Cag type IV secretion system activity). These results indicate that H. pylori can cause loss of proteins normally localized to the gastric corpus as well as diffuse delocalization of corpus-specific proteins, resulting in marked changes in the normal gastric molecular partitioning into distinct corpus and antrum regions.
2023-12-04 | PXD046333 | Pride
Project description:Helicobacter pylori are gram-negative bacteria that colonize the human stomach and are the major etiological factor in gastric carcinoma development. The aim of this work was to evaluate changes in gene expression in gastric cells induced by H. pylori.
2016-03-01 | GSE70394 | GEO
Project description:Helicobacter pylori (H. pylori) infects nearly half of the global population. H. pylori infection is associated with various gastric diseases and is a recognized causative factor for gastric cancer. The mechanisms underlying the persistent colonization of H. pylori and its role in the development and progression of gastritis-associated carcinogenesis remain unclear. To investigate the pathogenic mechanisms of H. pylori infection, we performed RNA sequencing (RNA-seq) on H. pylori-infected gastric epithelial cells and analyzed the gene expression patterns induced by H. pylori infection, aiming to provide critical insights for understanding its disease-driving pathways.
2025-04-29 | GSE295523 | GEO
Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 and Kx2 were also grown in cell media in the absence of cells. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Keywords: RNA Expression Array
2008-02-22 | GSE10261 | GEO
Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Keywords: RNA Expression Array
2008-02-22 | GSE10262 | GEO
Project description:Forkhead box (Fox) proteins constitute an evolutionarily conserved family of transcriptional regulators whose deregulations lead to tumorigenesis. However, their regulation and function in gastric cancer are unknown. Promoter hypermethylation occurs during Helicobacter pylori (H pylori)-induced gastritis, but whether the deregulated genes contribute to the multi-step gastric carcinogenesis remains unclear. FOXD3 was found to be hypermethylated in a mouse model of H pylori infection and possess tumor-suppressive functions in gastric cancer cell lines. In order to characterize the direct targets of FOXD3 that confer its actions, we performed ChIP-chip in N87 gastric cancer cell line which express low level of FOXD3 in the nuclei of a sub-population of cells. Promoter hypermethylation occurs during Helicobacter pylori (H pylori)-induced gastritis, but whether the deregulated genes contribute to the multi-step gastric carcinogenesis remains unclear. We used MethylCap-microarray to identify hypermethylated genes in a mouse model of H pylori infection.
2012-12-28 | GSE39490 | GEO
Project description:Helicobacter pylori are gram-negative bacteria that colonize the human stomach and are the major etiological factor in gastric carcinoma development. The aim of this work was to evaluate changes in gene expression in gastric cells induced by H. pylori. The human gastric carcinoma-derived cell line AGS was infected with H. pylori strain 60190 (ATCC 49503) for 24 hours. RNA was extracted from three independent experiments.
2016-03-01 | E-GEOD-70394 | biostudies-arrayexpress
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182357 | GEO
Project description:Promoter hypermethylation occurs in human gastric cancers, but whether the deregulated genes contribute to the multi-step Helicobacter pylori (H pylori)-induced gastric carcinogenesis remains unclear. We used Microarray-based Methylation Assessment of Single Samples (MMASS) to identify differential methylated genes in 10 human gastric cancer tissues.
2012-12-28 | GSE39599 | GEO