DNA_methylation_pancreas
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010002386 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Epigenetic modifications, particularly DNA methylation have been increasingly implicated in cancer. Although some genes display aberrant methylation in pancreatic cancer, a comprehensive global analysis is yet to be performed. To define the genome-wide pattern of DNA methylation in pancreatic ductal adenocarcinomas (PDAC), the methylation profile of 156 PDAC and 23 non-malignant pancreas was captured using high-density arrays. More than 90,000 CpG sites were significantly differentially methylated (DM) in PDAC relative to non-malignant pancreas, with pronounced alterations in a sub-set of 13,517 CpG sites. This sub-set of differentially methylated CpG sites segregated PDAC from non-malignant pancreas, regardless of tumour cellularity. As expected, PDAC hyper-methylation was most prevalent in the 5’ region of genes (including the proximal promoter, 5’UTR and CpG islands). From 3981 genes aberrantly methylated, approximately 36% showed significant correlation between methylation and mRNA expression levels. Pathway analysis revealed an enrichment of aberrant methylation in genes involved in key molecular mechanisms important to PDAC: TGF-β, WNT, Integrin signaling, Cell adhesion, Stellate cell activation and Axon guidance. Bisulfite amplicon deep sequencing and qRT-PCR expression analyses of axon guidance pathway genes SLIT2, SLIT3, ROBO1, ROBO3, SRGAP1, and MET suggested epigenetic suppression of SLIT-ROBO signaling and up-regulation of MET expression. Hypo-methylation of MET and ITGA2 correlated with high gene expression, which correlated with poor survival of PDAC patients. These data suggest that aberrant methylation plays an important role in pancreatic carcinogenesis affecting known core signaling pathways with important implications for disease pathophysiology and therapy. This dataset includes gene expression data from 103 primary tumour samples. 86 samples from this dataset have already been deposited into GEO (GSE36924), and has been duplicated here since the data has been processed differently. This data is also available through the International Cancer Genome Consortium (ICGC) Data Portal (http://dcc/icgc.org), under the project code: Pancreatic Cancer (QCMG, AU). Access to the restricted clinical data must be made through the ICGC Data Access Compliance Office (http://www.icgc.org/daco). This dataset contains gene expression array data from 103 primary pancreatic ductal adenocarcinoma samples. All samples have 1 biological replicate. These data have corresponding methylation 450K array data (GSE49149).
2014-05-05 | E-GEOD-50827 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53-/- mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN-signaling.
2020-10-18 | GSE134217 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53-/- mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN-signaling.
2020-10-15 | GSE134092 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53-/- mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN-signaling.
2020-10-15 | GSE134093 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis. Using methylated DNA immunoprecipitation (MeDIP)-chip analysis, we found that 161 genes that were specifically hypermethylated in PANC-1 cells. Among them, miR-615-5p was hypermethylated in its putative promoter region, which silenced its expression in PDAC cell lines. Comparison between PANC-1 cell lines and normal pancreas tissue
2013-09-01 | E-GEOD-44738 | biostudies-arrayexpress
Project description:<p>Cancer-associated fibroblasts (CAFs) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we employ single-cell RNA-sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human PDAC tumors. Six human PDAC tumor specimens from six patients were collected, and processed for single-cell RNA-sequencing analysis. Adjacent-normal pancreas tissue was also collected from two of the patients. Tumor samples were digested, and fluorescence-activated cell sorting was used to isolate viable cells. For one tumor sample, viable, CD45-negative, CD31-negative, and EpCAM-negative cells were also isolated to enrich for CAFs. The 10X Chromium platform was then used to isolate single cells for RNA-sequencing analysis. This work has demonstrated the differences in immune cell populations between adjacent-normal and tumor tissues, and identified subpopulations of epithelial cells and CAFs present in PDAC tumors. This high-throughput analysis is a resource to better understand the cell populations present in PDAC, and may ultimately aid in the development of more effective therapies for this deadly malignancy.</p>
| phs001840 | dbGaP
Project description:Cell conditioned medium from human pancreatic cancer cell lines MiaPaCa-2, AsPC-1, primary pancreatic cell lines as well as human FFPE tissue samples from pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), ampullary cancer, non-malignant adjacent pancreas and normal pancreas were analyzed via targeted (SRM, PRM) and/or explorative (DIA) mass spectrometry.
| MSV000090255 | MassIVE
Project description:We used microarrays to detail the global gene expression signature of PDAC and to identify distinct up- and down-regulated transcripts in pre-cancerous pancreatic tissue compared to control pancreas. We also established from this dataset the metabolic signature of pre-cancerous pancreas to define new metabolic therapeutic targets for PDAC.
2025-11-13 | GSE284155 | GEO
Project description:In this study we demonstrate that spheroids isolated from normal pancreas and co-trasplanted with PDAC orthotopically in mouse pancreas , inhibited tumor growth. Fibronectin proteolytic fragments generated by trypsin and released by pancreatic spheroids, were responsible for of the observed effect. Specifically, in vitro analysis revealed that FAK and FGFR1 signalling were turned off in tumor cells inducing tumor cell detachment, indicating a cooperative activity between the two signalling pathways. This mutual relationship was confirmed by the addition of FGF2 that reversed both FGFR1 and FAK defosphorilation and promoted PDAC cell adhesion and proliferation. Mass spectrometry proteomic analysis and the use of mAb allowed the identification of the FN fragments belonging to the Type III domain responsible of PDAC inhibition. Finally, the effect of FAK and FGFR signalling inhibitors was tested in combination both in vivo and in vitro to emulate the effect of normal pancreatic spheroids on PDAC growth.
2023-10-24 | PXD035770 | Pride