Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrative Analysis Defines Distinct Prognostic Subgroups of Intrahepatic Cholangiocarcinoma

ABSTRACT: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. It is defined by cholangiocytic differentiation and has poor prognosis. Recently, epigenetic processes have been shown to play an important role in cholangiocarcinogenesis. We performed an integrative analysis on 52 iCCAs using both genetic and epigenetic data with a specific focus on DNA methylation components. We identified four major iCCA subgroups with widespread genomic and epigenomic differences and prognostic implications. Furthermore, our data suggest differences in the cell-of-origin of the iCCA subtypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201241 | GEO | 2022/08/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Deconstruction of the immune microenvironment identifies tumor-, immune- and stroma-specific subtypes of intrahepatic cholangiocarcinoma

Project description:We have profiled by RNA-sequencing healthy livers and 4 distinct murine intrahepatic cholangiocarcinoma (iCCA) models to compare their molecular profile to the identified human STIM clusters of iCCA. Results: Comparative analysis indicated high molecular similarity between the KRAS/p19 model and the human Inflammatory stroma cluster while the other models resembled the Hepatic stem-like cluster.

2022-05-23 | GSE171443 | GEO

Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma

2015-01-22 | GSE63420 | GEO

Effect of Crenigacestat treatment in xenograft model of HUCCT1 intrahepatic cholangiocarcinoma

Project description:Intrahepatic Cholangiocarcinoma (iCCA) is a difficult type of cancer to diagnose, extremely aggressive and resistant to therapeutic options with an increased incidence and mortality over time. The overexpression of Notch pathway is implicated in iCCA to create an ecosystem that drives the tumor aggressiveness. Specifically, Notch1 is overexpressed in iCCA tissue of patients, playing an important role on tumor growth. Our purpose was to investigate the effectiveness of Crenigacestat in in vivo experiments, using Hucct1 injected in CD1 mice to generate an iCCA xenograft mouse model. In the present study, in order to explore modulated factors and genes by treatment we performed a transcriptomic analysis validated by Western Blotting and qRT-PCR on iCCA tumor masses of xenograft mice. Our results indicate that the treatment significantly inhibited Notch1 and HES1 genes and proteins triggering a strong immune response. Nevertheless, moderate fibrosis was shown in this model which may have hindered response to therapy to promote tumor progression. We used microarray technology to understand the molecular mechanisms affected by Crenigacestat in HUCCT1 xenograft model of intraepatic cholangiocarcinoma.

2022-04-27 | GSE150024 | GEO

Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma

Project description:Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome sequencing analyses we have discovered a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%). Methods: mRNA and gDNA were exctracted from fresh frozen tumor tissues and corresponding normal tissue (n=8 pairs) from patients with iCCA who underwent surgical resection. RNA-seq was performed using Illumina HiSeq 2500 System with 100 nucleotide single-end reads. One sample and its paired non-tumoral tissue were eliminated from the subsequent analysis because of bad RNa quality. The same 8 paired tumors were also analyzed by whole-exome seq. Submitter confirms there are no patient privacy concerns with these data. This dataset is part of the TransQST collection.

2015-01-22 | E-GEOD-63420 | biostudies-arrayexpress

Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma

Project description:Background and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features. Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes. Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.

2022-07-12 | GSE179443 | GEO

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

Project description:Cholangiocarcinoma (CCA) is a deadly tumour lacking effective therapies. Clinically-relevant experimental models and analysis of human samples represent the cornerstone of mechanistic cancer research. Thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats encompasses key histological and molecular features of human iCCA. Molecular studies in bile may capture carcinogenic alterations and therapeutic vulnerabilities in CCA. We performed bile proteomic and metabolomic analyses in this model leading us to identify unrecognized mechanisms relevant to human iCCA.

2022-06-09 | PXD032802 | Pride

Applications of Next Generation Sequencing in intrahepatic cholangiocarcinoma

Project description:We generated 100 M of high-quality sequencing reads (~10 M per sample) and catalogued the expression profiles of 1643 microRNA in each sample. The analysis showed differences of microRNAs between intrahepatic cholangiocarcinoma and normal bile duct tissues.

2019-12-10 | GSE93366 | GEO

Effect of NOTCH-γ-secretase inhibitor LY3039478 therapy on patient derived xenograft (PDX) mouse model of intrahepatic cholangiocarcinoma

Project description:Intrahepatic Cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. Recently, aberrant Notch signaling was reported in iCCA carcinogenesis. Specifically, altered expression and/or activation of the receptors Notch1/2 suggests a role for Notch pathway overactivation during iCCA formation and progression. In this study, we examined the effects of Notch inhibition by γ-secretase inhibitor, LY3039478 in human iCCA cell lines and in an excellent patient derived-xenograft (PDX) model. Expression of several Notch pathway components, including NICD, Hes1, and DLL4, were reduced after GSI treatment. Moreover, LY3039478 inhibits cell migration and invasion while in GSI-treated mice, tumor growth was delayed compared to vehicle and chemotherapy. These results support the notion that Notch inhibition by GSI may reduce in vivo tumorigenesis. In addition, GSI reduces in PDX model VEGFA and MMP13 involved in capillary tube formation and tumor progression. Here, we therefore show a link between the efficacy of Notch inhibition and the tumor microenvironment through LY3039478 that slows tumor progression compared to control mice blocking angiogenesis via MMP13 downregulation. We used microarray technology to understand the molecular mechanisms affected by LY3039478. Cholangiocarcinoma PDX model was employed in this analysis.

2020-07-27 | GSE134114 | GEO

Integrative molecular and clinical analysis of intrahepatic cholangiocarcinoma reveals two prognostic subclassees

Project description:Intrahepatic cholangiocarcioma has two molecular classification of intrahepatic CCA with distinct clinical, pathological, biological and prognostic differences

2018-12-01 | GSE107943 | GEO

Gene expression profiles of bulk tumor tissues of intrahepatic cholangiocarcinoma

Project description:We report the gene expression profiles of bulk tumor tissues of intrahepatic cholangiocarcinoma

2020-12-30 | GSE162396 | GEO