Project description:To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility We performed an exome chip-based array study in 329 gastric cancer cases and 683 controls.
Project description:To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility
Project description:Although blood-based protein biomarkers have been described for diagnosis of some cancers, detection of tumor-derived peptides/proteins in urine provides an attractive and non-invasive alternative for diagnostic or screening purposes. For instance, bladder tumor antigen (BTA) assay is FDA approved urine-based biomarker assay to detect the bladder cancer. In this study, we decided to investigate the possibility of discovering proteins as biomarkers in urine from individuals diagnosed with gastric cancer. We carried out comprehensive quantitative profiling of urine samples using tandem mass tags (TMT)-based multiplexed mass spectrometry approach. Of the 1,504 total number of proteins identified, 246 proteins were differentially expressed in a gastric cancer cohort. Ephrin A1 (EFNA1), pepsinogen A3 (PGA3) and vitronectin (VTN) were among the upregulated proteins which are known to play crucial role in the progression of gastric cancer. Notably, our analysis also revealed other overexpressed proteins including shisa family member 5 (SHISA5), mucin like 1 (MUCL1) and leukocyte cell derived chemotaxin 2 (LECT2), which had not previously been linked to gastric cancer. We decided to deploy a recently developed targeted method, SureQuant, for validating a subset of potential proteins discovered in this study. We confirmed the overexpression of EFNA1, VTN and SORT1 in an independent set of urine samples. Our study demonstrates the potential of urinary proteomics to identify promising diagnostic biomarkers of cancers in a non-invasive fashion.
Project description:To identify chromatin alterations in primary gastric adenocarcionomas, we performed nano-scale chromatin immunoprecipitation-sequencing (Nano-CHiPseq) of histone modifications in 5 gastric cancers and matched normal tissues, We identified hundreds of somatically-altered promoters (marked by H3K4me3) and enhancers (H3K4me1). The majority of cancer-associated promoters localized to genomic sites lacking previously-annotated transcription start sites (“cryptic promoters”), driving high expression of nearby genes implicated in gastrointestinal cancers, embryonic development, and tissue specification. Our findings demonstrate the feasibility of performing chromatin profiling on solid tumors where tissue is limiting, to identify in non-coding regions regulatory elements, transcriptional patterns and genetic variants associated with cancer. We propose a pervasive role for cryptic promoters in the reactivation of early developmental programs in gastric cancer, and the potential utility of cryptic promoters as biomarkers of malignancy. Five gastric cancer tumor normal pairs are profiling in multiple number of chromatin marks
Project description:Cancer Gastric (CG) is a multifactorial disease with an important genetics background, per example copy number variants (CNV). Microarray data analysis were performed to identify CNV that could be contributing to those Mexican patient's clinical phenotypes
Project description:EGFR and E-cadherin are key genes closely related with gastric cancer. EGFR overexpression while E-cadherin deletion are characteristic partners in certain types of gastric cancer. Discovering their co-regulatory mechanisms will contribute to provide molecular basis and newer therapeutic strategy for this type of gastric cancer.In this study, E-cadherin overexpression and EGFR knockdown were performed in gastric cancer cells, and their effects on cell growth and metastasis were confirmed. Gene microarrays were used to analyze the changes of gene expression profile. A group of molecular targets co-regulated by EGFR and E-cadherin were found, including lncRNAs, circRNAs and mRNAs. Total 1204 DEGs are related to EGFR knockdown, while 3882 DEGs related to E-cadherin overexpression. Among their downregulated mRNAs, GLI2 and CEACAM6 were identical targets with most significance. Furthermore, 274 overlapping DEGs were screened as potential co-regulatory targets of EGFR and E-cadherin.With GLI2 and CEACAM6 as co-targets, we mapped two representative ceRNA networks to throw light on the co-regulation mechanism of EGFR and E-cadherin in regulating gastric cancer cells.
Project description:Human primary gastric cancer tissue SAGE libraries. Profile of the genes expressed in well and poorly differentiated gastric cancer, early and advanced gastric cancer, scirrhous type gastric cancer, and lymph node metastasis determined through SAGE. Keywords = gastric cancer, histology, early gastric cancer, advanced gastric cancer, lymph node metastasis, scirrhous type gastric cancer Keywords: other
Project description:To identify chromatin alterations in primary gastric adenocarcionomas, we performed nano-scale chromatin immunoprecipitation-sequencing (Nano-CHiPseq) of histone modifications in 5 gastric cancers and matched normal tissues, We identified hundreds of somatically-altered promoters (marked by H3K4me3) and enhancers (H3K4me1). The majority of cancer-associated promoters localized to genomic sites lacking previously-annotated transcription start sites (“cryptic promoters”), driving high expression of nearby genes implicated in gastrointestinal cancers, embryonic development, and tissue specification. Our findings demonstrate the feasibility of performing chromatin profiling on solid tumors where tissue is limiting, to identify in non-coding regions regulatory elements, transcriptional patterns and genetic variants associated with cancer. We propose a pervasive role for cryptic promoters in the reactivation of early developmental programs in gastric cancer, and the potential utility of cryptic promoters as biomarkers of malignancy.
Project description:Chronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in a majority of individuals. We report here that the C57Bl6 mouse model of experimental infection with the closely related H. felis recapitulates this wide range in host susceptibility. A majority of infected mice develop premalignant lesions such as gastric atrophy, compensatory epithelial hyperplasia and intestinal metaplasia, whereas a minority is completely protected from preneoplasia. Protection is associated with the failure to mount an IFN-gamma response to the infection and an associated high Helicobacter burden. We demonstrate that IFN-gamma is essential for clearance of Helicobacter, but also mediates the formation of preneoplastic lesions. We further provide evidence that IFN-gamma triggers a specific transcriptional program in murine gastric epithelial cells in vitro and in vivo, and induces their preferential transformation to the hyperplastic phenotype. In summary, our data suggest a dual role for IFN-gamma in Helicobacter pathogenesis that could provide an explanation for the differential susceptibility to H. pylori-induced gastric pathology in the human population. Keywords: response to in vitro stimulus / comparison of histopathological states We chose mice for gene expression profiling that following Helicobacter infection had (a) symptoms of gastritis, but no epithelial changes, (b) atrophic gastritis accompanied by corpus gland hyperplasia or (c) atrophic gastritis accompanied by intestinal metaplasia. An uninfected control group was also included in the analysis, as were two groups of mice that lacked mature T- and B-cells due to a deletion mutation in the rag1 gene (Rag-1-/-) and that were either experimentally infected or served as Rag-1-/- uninfected controls. To see the effects of IFNg on murine gastric epithelial cells we analysed an immortalized murine primary gastric epithelial cell line treated with three different concentrations of IFNg in comparison to an untreated control.