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Unknown,Transcriptomics,Genomics,Proteomics

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Human cholangiocarcinoma (CC), ECC (extrahepatic CC) and ICC (intrahepatic CC) cases versus control

ABSTRACT: CpG island methylation profiling of human cholangiocarcinoma, ECC and ICC, cases compared to matched normal controls or to pools of corresponding normal controls. Goal was to identify cholangiocarcinoma-specific differentially methylated regions (DMRs). Highly methylated DNA from cases and controls was enriched by methyl CpG-immunoprecipitation (MCIp) and co-hybridized. DMRs were defined by stepwise stringent criteria such as selecting top 5% vicinal array probes only. ECC- and ICC-specific and common DMRs were identified.

ORGANISM(S): Homo sapiens

SUBMITTER: Dieter Weichenhan

PROVIDER: E-GEOD-44965 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway.

Goeppert Benjamin B Konermann Carolin C Schmidt Christopher Roman CR Bogatyrova Olga O Geiselhart Lea L Ernst Christina C Gu Lei L Becker Natalia N Zucknick Manuela M Mehrabi Arianeb A Hafezi Mohammadreza M Klauschen Frederick F Stenzinger Albrecht A Warth Arne A Breuhahn Kai K Renner Marcus M Weichert Wilko W Schirmacher Peter P Plass Christoph C Weichenhan Dieter D

Hepatology (Baltimore, Md.) 20131224 2

<h4>Unlabelled</h4>The molecular mechanisms underlying the genesis of cholangiocarcinomas (CCs) are poorly understood. Epigenetic changes such as aberrant hypermethylation and subsequent atypical gene expression are characteristic features of most human cancers. In CC, data regarding global methylation changes are lacking so far. We performed a genome-wide analysis for aberrant promoter methylation in human CCs. We profiled 10 intrahepatic and 8 extrahepatic CCs in comparison to non-neoplastic b ...[more]

PMID: 24002901

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Human cholangiocarcinoma (CC), ECC (extrahepatic CC) and ICC (intrahepatic CC) cases versus control

Project description:CpG island methylation profiling of human cholangiocarcinoma, ECC and ICC, cases compared to matched normal controls or to pools of corresponding normal controls. Goal was to identify cholangiocarcinoma-specific differentially methylated regions (DMRs).

2016-02-26 | GSE44965 | GEO

Transcription profiling by array of human Intrahepatic Cholangiocarcinoma (ICC) and Combined Hepatocellular Cholangiocarcinoma (CHC) tumors

Project description:We compared transcriptomic profiles of 23 ICC tumor specimens to hepatocellular carcinoma (HCC) specimens using Affymetrix mRNA array and the miRNA array platforms to search for unique gene signatures linked to patient prognosis. ICC and HCC share common stem-like molecular characteristics and stem-like tumor features associated with poor prognosis. Gene expression profiling of 16 intrahepatic cholangiocarcinoma (ICC), 7 mixed type of combined HCC and ICC (CHC), 2 Hepatic Adenoma, 5 Focal Nodular Hyperplasia, and 7 Non-Tumor Tissues were performed.

2012-09-28 | E-GEOD-32879 | biostudies-arrayexpress

RNA sequencing data of differentially treated cancer associated fibroblast, myeloid-derived supression cells, and ICC tumor cells in ICC patient

Project description:An interactive tumor microenvironment with different stromal cell types is necessary for supporting cancer stemness. Cancers with dense fibrotic stroma such as intrahepatic cholangiocarcinoma (ICC) are often highly aggressive and chemotherapy resistance. Here, we show that cancer associated fibroblasts (CAF) greatly enhances the capacity of blood CD33+ myeloid-derived suppressor cells (MDSCs) to promote stem-like properties in ICC cells and tumor growth via paracrine signaling. Mechanistically, CAF mediates hyperactivated 5-LO pathway in CD33+ MDSCs via secretion of IL-6 and IL-33, resulting in overproduction of LTB4, which acts on BLT2 to promote cancer stemness via Akt-mTOR signaling. hyperactivated 5-LO pathway are observed in tumor-infiltrating CD33+ MDSCs compared with blood counterparts from the same ICC patients. Moreover, BLT2 blockade augments chemotherapeutic efficacy in ICC PDX models. Thus, our study reveals a previously unrecognized stromal cell network in which CAF educate myeloid cells to shape the optimal supportive microenvironment for the aggressive nature of ICC.

2022-01-01 | GSE158755 | GEO

Transcriptional expression of ICC-DMP and ICC-MY in murine small intestine

Project description:Interstitial cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine ICC are gathered in the region of the myenteric plexus (ICC-MY) and within the deep-muscular plexus near the submucosal surface of the circular muscle layer (ICC-DMP). These two classes of ICC have different physiological functions. ICC-MY are pacemaker cells and generate the slow wave electrical rhythmicity of gastrointestinal organs. ICC-DMP form synaptic connections with the varicose nerve terminals of enteric motor neurons and are involved in reception and transduction of motor neurotransmission. In the present study we used recently developed highly selective techniques to isolate the two classes of ICC from enzymatically dispersed intestinal muscles by fluorescence-activated cell sorting. Transcriptional expression of the two functional classes was investigated using DNA microarray analysis. Keywords: comparative transcriptional profiling

2007-11-29 | GSE7809 | GEO

RNA-seq of FGFR2 fusion+ ICC cell lines (ICC21 and ICC10-6) treated with Infigratinib or/and Afatinib against untreated control

Project description:Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC), a deadly bile duct malignancy. FGFR kinase inhibitors (FGFRi) have shown promising efficacy against FGFR2+ ICC in clinical trials, leading to the regulatory approval of the ATP-competitive FGFR inhibitors, pemigatinib and infigratinib (BGJ398), for this subset of patients who failed standard treatment . However, the objective response rate (ORR) for each FGFR inhibitor (FGFRi) studied to date in FGFR2+ ICC is <45% and disease progression invariably arises within ~6-12 months. By employing high-throughput drug screens and signaling studies, we identified signaling feedback via the EGFR pathway as a major mediator of adaptive resistance to FGFR kinase inhibition in a set of patient-derived ICC models. To further gain insights into the synergistic effects of the EGFR/FGFR combination and address the mechanisms underlying the survival pathway reactivation, we performed RNA sequencing in our FGFR-driven ICC models (ICC21 and ICC10-6). For these studies, we treated FGFR2 fusion+ ICC cell lines ICC21/ICC10-6 with four conditions (DMSO/Infigratinib/Afatinib/Combo) for 4 hours followed by RNA sequencing.

2024-03-21 | E-MTAB-11324 | biostudies-arrayexpress

Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome

Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.

2022-02-16 | PXD021821 | Pride

Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [miRNA]

Project description:We compared transcriptomic profiles of ICC tumor specimens to hepatocellular carcinoma (HCC) specimens using Affymetrix mRNA array and the miRNA array platforms to search for unique gene signatures linked to patient prognosis. ICC and HCC share common stem-like molecular characteristics and stem-like tumor features associated with poor prognosis. Gene expression profiling of 16 intrahepatic cholangiocarcinoma (ICC), 7 mixed type of combined hepatocellular cholangiocarcinoma (CHC), 2 Hepatic adenoma, 3 focal nodular hyperplasia (FNH), 5 non-tumor liver tissues, and 2 CCA cell lines were performed.

2012-09-28 | E-GEOD-32957 | biostudies-arrayexpress

Transcriptome analysis of a FACS-sorted human intersitial cells of Cajal (ICC) [array]

Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Gastrointestinal stromal tumors (GIST) arise within the ICC lineage due to activating KIT/PDGFRA mutations. In this study we developed a method for isolation of human ICC by immunolabeling and fluorescence-activated cell sorting (FACS). Briefly, human gastric musculature was dissociated and incubated with antibodies against CD45, FCER1A, CD11B, KIT, and CD34. ICC (defined as HP-KIT+CD34- cells), NOT ICC (defined as HP-KIT-CD34- cells), and hematopoietic (HP) cells (defined as HP+ cells) were isolated using FACS. Microarray was performed on ICC, NOT ICC, HP+ cells, and unfractionated gastric tunica muscularis. This study utilized micorarray for the phenotypic characterization of FACS-sorted human ICC, allowing comparison of ICC to other cells of the gastric musculature, including GIST. De-identified human gastric tissues obtained as surgical excess tissue from patients undergoing bariatric operations. This study utilized oligonucleotide microarray analysis to characterize the transcriptome of FACS-sorted human ICC.

2017-02-22 | GSE77839 | GEO

Single-cell and Spatial Architecture of Primary Liver Cancer

Project description:Using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) from a high-resolution perspective.

2024-01-26 | PXD044778 | Pride

Methylation screening of reciprocal genome-wide UPDs identifies novel human specific imprinted genes

Project description:Utilizing reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotypes, we have analyzed ~0.1% of CpG dinucleotides present in the human genome for imprinted differentially methylated regions (DMRs) using the Illumina Infinium HumanMethylation27 BeadChip microarray. This approach identified 15 imprinted DMRs associated with previously characterized imprinted domains, and confirmed the maternal methylation of the RB1 DMR. In addition, we discovered two novel DMRs: a maternally methylated region overlapping the FAM50B promoter CpG island, which results in paternal expression of this retrotransposon, and a paternally methylated region located between maternally expressed ZNF597 and NAT15 genes.

2011-05-26 | GSE28525 | GEO

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