Identification of CLDN6 as a novel tumor-promoting gene in gastric cancer
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ABSTRACT:
PROVIDER: PRJNA544946 | ENA |
REPOSITORIES: ENA
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Project description:We identified CLDN6 as a novel tumor-promoting gene in gastric cancer (GC). To clarify the mechanism of tumor promoting by CLDN6, we analyzed the transcriptomic difference between control and CLDN6 knockdown GC cells.
2020-06-01 | GSE131787 | GEO
Project description:The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa. Our results revealed a common ECM signature composed of 142 proteins and indicated that gastric carcinogenesis encompasses ECM remodeling through alterations in the abundance of 24 components, mainly basement membrane proteins. Indeed, we could only identify one de novo tumor-specific protein, the collagen alpha-1(X) chain (COL10A1). Functional analysis of the data demonstrated that gastric ECM remodeling favor tumor progression by activating ECM receptors and cellular processes involved in angiogenesis and cell-extrinsic metabolic regulation. By analyzing mRNA expression in an independent GC cohort available at the TGCA, we validated the expression profile of 12 differentially expressed ECM proteins. Importantly, the expression of COL1A2, LOX and LTBP2 significantly correlated with high tumor stage, with LOX and LTBP2 further impacting patient overall survival. Our results contribute for a better understanding of GC biology and highlight the role of core ECM components in gastric carcinogenesis and their clinical relevance as biomarkers of disease prognosis.
2022-05-20 | PXD029782 | Pride
Project description:Copy number profiling of 27 gastric cancer cell lines and 105 gastric tumor tissues. we hypothesized that a detailed fine-scale survey of genomic CNAs might reveal potential genes disrupted by fusion events in gastric cancer. We inferred the locations of likely chromosomal breakpoints by identifying regions where closely-spaced microarray probes exhibited striking transitions in copy number. 27 gastric cancer cell lines and 105 gastric tumor tissues were profiled by Agilent 244K microarray.
2010-12-31 | E-GEOD-22694 | biostudies-arrayexpress
Project description:GPAT3 is a novel inflammatory protein promoting gastric bacterial colonization and gastritis in Helicobacter pylori infection
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Project description:The biological behavior and clinical outcome of gastric cancers are variable considerably according to anatomic location, such as proximal gastric cancer (PGC) and distal gastric cancer (DGC). Therefore, identification of the biomarkers used for recognizing the biological behavior and predicting clinical outcome has been a major goal in gastric cancer researches.
2013-03-27 | E-MTAB-1307 | biostudies-arrayexpress
Project description:Bacterial-modulated gastric epithelial cells (GECs) play key roles in H. pylori-associated pathology. Here we demonstrate a pro-colonization and pro-inflammation role of GEC-expressed glycerol-3-phosphate acyltransferase 3 (GPAT3), a lipid metabolism-associated protein, in H. pylori infection. GPAT3 expression was elevated in gastric mucosa of both patients and mice infected with H. pylori. GPAT3 in GECs was synergistically induced by H. pylori and IL-22 in a cagA-dependent manner. Human gastric GPAT3 correlated with H. pylori colonization and the severity of gastritis, and mouse GPAT3 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il22-/-, Gpat3-/- and Il22-/-Gpat3-/- mice. Mechanistically, GPAT3 directly interacted with CCAR1 and activated IKKγ, subsequently promoted NF-κB phosphorylation whereby NF-kB directly bound to the promoters of MMP1, CXCL11 and IL-33 to activate their transcription, which not only led to decreased E-cadherin and zonula occludens-1 proteins by MMP1, thereby resulting in gastric mucosal damage and increased H. pylori colonization; but also resulted in increased gastric influx of CD8+ T cells via CXCL11-dependent migration and their subsequent IL-33-dependent IFN-γ production, thereby promoting H. pylori-associated gastritis. Overall, we propose a model in which GPAT3 collectively ensures H. pylori persistence and promotes gastritis.
2024-04-26 | GSE264450 | GEO
Project description:Histone deacetylation is involved in epigenetically mediated tumor suppressor genes silencing. The screen of genes modulated by histone acetylation in gastric cancer maycontribute to the identification of potential therapeutic targets. In this experiment we aimed to identify differentially expressed genes by comparing Trichostatin A (TSA)-treated and non-treated gastric cancer cell lines. TrichostatinA (TSA) belongs to the hydroxamic acid chemical class histone deacetylaseinhibitors, which selectively inhibit the class I and II mammalian histonedeacetylase families. As expected, TSA acetylates promoter regions, or disables corepressors, resulting in increased gene expression. The ACP02 and ACP03 gastric cancer cell lines used in this experiment were previously established by our research group from primary gastric adenocarcinomas classified as diffuse and intestinal types, respectively. Both cell lines present chromosome 8 trisomy, MYC amplification, and TP53 loss of copy. Moreover, ACP03 is able to start a tumorigenesis process in Cebus apellas.
2016-10-21 | E-MTAB-4736 | biostudies-arrayexpress
Project description:Reliable identification of cancer markers can have substantial implications to early detection of cancer. We report here an integrated computational and experimental study on identification of gastric cancer markers in patients’ tissue and sera based on (i) genome-scale transcriptomic analyses on 80 paired gastric cancer/reference tissues, with the aim of identifying abnormally expressed genes at various subtypes/stages of gastric carcinoma (ii) a computational identification of differentially expressed genes that may have their proteins secreted into blood circulation, followed by experimental validations. 160 Total samples were analyzed on paried tumor and adjacent normal tissues from 80 gastric cancer patients. Differential analysis identified genes with a fold-change over 1.5.
2011-03-01 | E-GEOD-27342 | biostudies-arrayexpress
Project description:Primary human gastric cancer-associated fibroblast (CAF) cultures (CAF14 and CAF32) were establised from 2 gastrectomy specimens. Silencing the expression (loss-of-function effect) of Twist1 in CAFs showed candidate target genes regulated by Twist1 and abrogated their tumor-promoting properties. Experiment design: two gastric CAFs (CAF14 adn CAF32, respectively) were establised from two gastric cancer patients and Twist1 knockdown studies were performed using shRNA.
2014-10-28 | E-GEOD-62738 | biostudies-arrayexpress
Project description:Identification of Genes Promoting Resistance to Enzalutamide
| PRJNA659253 | ENA