Methylome and transcriptome of EAC (expression)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72873 | GEO | 2016/05/01
SECONDARY ACCESSION(S): PRJNA295228
REPOSITORIES: GEO
Similar Datasets
Project description:genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett’s, 64 normal adjacent squamous and 21 normal stomach. Transcriptome data was performed for 70 samples with methylation profile (48 EAC, 4 Barrett’s and 18 normal adjacent squamous). This is the first study to use methylome, transcriptome and ENCODE data to characterize the regulatory role of methylation in EAC.
2016-05-01 | GSE72872 | GEO
Project description:Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett’s esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarray) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene families are the most frequently represented gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate squamous, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation analysis. While this method was satisfactory for discriminating squamous and BE, it demonstrates the need for more detailed investigations into profiling changes within BE leading to the progression towards EAC. A comparison of three esophageal biopsy groups from separate individuals: normal squamous (n=9), Barrett's esophagus without dysplasia (n=22) & adenocarcinoma (n=23). Adenocarcinoma samples overlap with members of DNA copy number analysis GEO series GSE10506 such that, in each case genomic DNA and total RNA were extracted from the same biopsy. The matching copy number data GEO samples IDs are noted in characteristics: Matching CN Sample ID
2011-08-16 | E-GEOD-28302 | biostudies-arrayexpress
Project description:Esophageal adenocarcinoma (EAC) has the fastest increase of any cancer in the US and Europe, and arises in the setting of Barrett’s esophagus (BE), defined by replacement of normal squamous epithelium with columnar intestinal-like epithelium. BE is thought to result from chronic esophageal inflammation but has been elusive to model in animals. Herein, we have generated the first transgenic mouse model of Barrett’s esophagus through overexpression of interleukin-1ß (IL-1β). IL-1β overexpression in the mouse esophageal mucosa induces chronic inflammation that progresses to intestinal metaplasia, with characteristic expression of TFF2, Bmp4 and Cdx2. With aging, IL-1b transgenic mice progress to esophageal adenocarcinoma (EAC) but the process is markedly accelerated by exposure to bile acids and/or nitrosamines, resembling the human counterpart. Moreover, progenitor cells present in the gastric cardia, but absent from the esophagus in humans and mice, are increased in BE, suggesting the cell of origin in the gastric cardia
2011-01-31 | GSE24931 | GEO
Project description:In the present study, we applied deep, quantitative mass-spectrometry to clinical samples (Barrett’s esophagus and matched adjacent normal biopsies) to gain a mechanistic understanding of the molecular pathways associated with disease progression. From our rich LC/MS profiles, we identified a robust proteomic signature that was able to correctly classify independent samples on disease status. Projection of this same signature against EAC tumor profiles was strongly predictive of survival outcomes, while subsequent comparative analysis with published BE transcriptomic profiles provided independent evidence in support of these results. Further, our phosphoproteomic analysis revealed signaling pathways specifically and significantly altered in BE relative to paired controls, providing some mechanistic insights into the cellular dysregulation of key components of specific processes that likely drives disease progression.
2022-08-11 | PXD023293 | Pride
Project description:Methylome and transcriptome of EAC
| PRJNA295227 | ENA
Project description:Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett’s esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarray) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene families are the most frequently represented gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate squamous, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation analysis. While this method was satisfactory for discriminating squamous and BE, it demonstrates the need for more detailed investigations into profiling changes within BE leading to the progression towards EAC.
2011-08-17 | GSE28302 | GEO
Project description:Background & Aims: Tissue metaplasia is uncommon in adults because established cis-element programs resist rewiring. In Barrett’s esophagus, the distal esophageal mucosa acquires predominantly intestinal character, with notable gastric features, and is predisposed to develop invasive cancers. We sought to understand the chromatin underpinnings of Barrett’s metaplasia and why it commonly displays simultaneous gastric and intestinal properties. Methods: We profiled cis-regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Mutations in Barrett’s esophagus were examined in relation to tissue-specific enhancer landscapes using a random-forest machine learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett’s biopsy specimens using the assay for transposase-accessible chromatin (ATAC-seq). We used one- and two-color immunohistochemistry to examine protein expression of tissue-restricted genes. Results: Barrett’s esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis-elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett’s metaplasia co-express gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins, CLDN18, and a novel gastric marker, ANXA10, revealed extensive tissue and sub-clonal heterogeneity of dual stomach-intestinal cell states. Conclusions: These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett’s esophagus. Pervasive intra-gland variation argues against stem-cell governance of this phenotype.
2021-06-03 | GSE97178 | GEO
Project description:Esophageal adenocarcinoma (EAC) is a common and aggressive type of cancer and Barrett’s esophagus (BE) is a known precursor lesion and the strongest risk factor for EAC. Prediction of risk is currently based on histologic examination which is challenged by problems such as inter-observer variability due to high heterogeneity of the dysplastic tissue. Molecular markers might offer an additional way to understand carcinogenesis and improve diagnosis and eventually treatment. .
2021-09-09 | PXD020903 | Pride
Project description:Barrett’s esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC). To detect EAC in early stage, patients with BE undergo endoscopic surveillance. Surveillance cohorts largely consist of non-dysplastic Barrett’s esophagus (NDBE) patients with a low annual progression risk (<0.5%). Predictive biomarkers for malignant progression of NDBE could improve efficacy of surveillance. Biomarker research has mostly focused on aberrant protein expression on BE epithelial cells. Moreover, insight in cell signaling driving malignant transformation is unknown. This study uses a data-driven approach to analyze tumor-stroma interaction in NDBE which progressed to high grade dysplasia (HGD) or EAC.
2023-01-08 | GSE210647 | GEO
Project description:Despite continual efforts to rationalize a prognostic stratification of patients with esophageal adenocarcinoma (EAC) before treatment, current staging system only shows limited success owing to the lack of molecular and genetic markers that reflect prognostic features of the tumor. To develop molecular predictors of prognosis, we used systems-level characterization of tumor transcriptome. Using DNA microarray, genome-wide gene expression profiling was performed on 75 biopsy samples from patients with untreated EAC. Various statistical and informatical methods were applied to gene expression data to identify potential biomarkers associated with prognosis. Potential marker genes were validated in an independent cohort using quantitiative RT-PCR to measure gene expression. Distinct subgroups of EAC were uncovered by systems-level characterization of tumor transcriptome. We also identified a six-gene expression signature that could be used to predict overall survival (OS) of EAC patients. In particular, expression of SPARC and SPP1 was a strong independent predictor of OS, and a combined gene expression signature with these two genes was associated with prognosis (P < 0.024), even when all relevant pathological variables were considered together in multivariate Cox hazard regression analysis. Our findings suggest that molecular features reflected in gene expression signatures may dictate the prognosis of EAC patients, and these gene expression signatures can be used to predict the likelihood of prognosis at the time of diagnosis and before treatment. 64 primary esophageal adenocarcinoma, 15 Barrett's esophagus and 28 surrounding normal fresh frozen tissues were used for microarray. All the tissues were obtained after curative resection after pathologic confirm at UT M.D. Anderson Cancer Center (MDACC). Microarray experiment and data analysis were done in the Dept. of systems biology at MDACC DNA microarray (Illumina human V2)
2011-01-04 | E-GEOD-13898 | biostudies-arrayexpress