Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A β-catenin-regulated RNA processing transcriptional program imposes chemotherapy resistance and predicts T-ALL patient survival associated with high BRCA1 levels [RNA-Seq]

ABSTRACT: De novo acquisition or subclonal selection of chemotherapy resistant cell populations are at the base of relapse in cancer. We have now investigated the role of ß-catenin in the evolution of T-ALL patients. We identified an RNA-processing signature that is directly regulated by ß-catenin in T-ALL cell lines. This signature was sufficient to identify T-ALL patients with poorest prognosis, together with high ß-catenin levels in an outdated discovery cohort with high incidence of refractory patients. In an independent validation cohort of T-ALL patients treated with current protocols and a 5-years survival >90%, neither ß-catenin-dependent signatures nor ß-catenin mRNA levels were predictive of patient outcome. However, further analysis of data demonstrated the prognosis value of the ß-catenin RNA-processing signature specifically in tumors carrying high BRCA1 levels. Finally, we show that both ß-catenin and BRCA1 enhanced the recovery of T-ALL cells after chemotherapy thus providing a mechanistic explanation for the prognosis value of ß-catenin and BRCA1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196985 | GEO | 2022/12/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A β-catenin-regulated RNA processing transcriptional program imposes chemotherapy resistance and predicts T-ALL patient survival associated with high BRCA1 levels [ChIP-Seq]

Project description:De novo acquisition or subclonal selection of chemotherapy resistant cell populations are at the base of relapse in cancer. We have now investigated the role of ß-catenin in the evolution of T-ALL patients. We identified an RNA-processing signature that is directly regulated by ß-catenin in T-ALL cell lines. This signature was sufficient to identify T-ALL patients with poorest prognosis, together with high ß-catenin levels in an outdated discovery cohort with high incidence of refractory patients. In an independent validation cohort of T-ALL patients treated with current protocols and a 5-years survival >90%, neither ß-catenin-dependent signatures nor ß-catenin mRNA levels were predictive of patient outcome. However, further analysis of data demonstrated the prognosis value of the ß-catenin RNA-processing signature specifically in tumors carrying high BRCA1 levels. Finally, we show that both ß-catenin and BRCA1 enhanced the recovery of T-ALL cells after chemotherapy thus providing a mechanistic explanation for the prognosis value of ß-catenin and BRCA1.

2022-12-12 | GSE180650 | GEO

β-catenin activity induces an RNA biosynthesis program promoting therapy resistance in T Acute Lymphoblastic Leukemia

Project description:Understanding the molecular mechanisms that contribute to the appearance of chemotherapy resistant cell populations is necessary to improve cancer treatment. We have now investigated the role of β-catenin/CTNNB1 in the evolution of T-Acute Lymphoblastic Leukemia (T-ALL) patients and its involvement in therapy resistance. We have identified a specific gene signature that is directly regulated by β-catenin, TCF/LEF factors and ZBTB33/Kaiso in T-ALL cell lines, which is highly and significantly represented in 5 out of 6 refractory patients from a cohort of 40 children with T-ALL. By subsequent refinement of this gene signature, we found that a subset of β-catenin target genes involved with RNA-processing function are sufficient to segregate T-ALL refractory patients in three independent cohorts. We demonstrate the implication of β-catenin in RNA and protein synthesis in T-ALL and provide in vitro and in vivo experimental evidence that β-catenin is crucial for the cellular response to chemotherapy, mainly in the cellular recovery phase after treatment. We propose that combination treatments involving chemotherapy plus β-catenin inhibitors will enhance chemotherapy response and prevent disease relapse in T-ALL patients.

2022-12-12 | GSE196986 | GEO

Expression data from mouse embryonic stem cells

Project description:Analysis of the transcriptome of ß-catenin flox/- mES cells in comparison with ß-catenin null mES cells or ß-catenin null mES cells stably transfected with an E-cadherin-?-catenin fusion protein. Expression assay was performed using the Affymetrix GeneChip Mouse Gene 1.0 ST array. The experiment includes ß-catenin flox/-, ß-catenin null and ß-catenin null E? mouse embryonic stem cells with three biological replicates for each sample.

2013-05-03 | E-GEOD-44543 | biostudies-arrayexpress

Stabilization of ß-catenin during murine Kidney Development

Project description:We define a pathogenic role for a ß-catenin-activated genetic pathway in murine renal dysplasia. Cre-mediated stabilization of ß-catenin in the ureteric cell lineage prior to the onset of kidney development increased ß-catenin levels and caused renal aplasia or severe hypodysplasia. A genome-wide analysis of mRNA expression in dysplastic tissue identified down-regulation of genes required for ureteric branching and up regulation of Tgfß2 and Dkk1. Hoxb7-Cre:EGFP mice ( Zhao, et al. (2004) Dev Biol 276:403-415) were crossed with mice containing loxP sites flanking exon 3 of the ß-catenin allele (ß-catdelta3/delta3) (Harada,et al. (2002) Cancer Res 62:1971-1977) to generate ß-catenin gain-of-function mutant mice specific to the uteric bud, termed ß-catGOF-UB .Eighteen ß-catGOF-UB mutant kidneys and 9 WT kidneys were micro-dissected at E12.5. Mutant kidneys were divided into three random pools (n=3) consisting of 6 kidneys each and mRNA expression assessed by microarray.

2011-03-28 | E-GEOD-20325 | biostudies-arrayexpress

Heterogenous radiomics patterns are associated with poor survivals and dysregulated pathways in medulloblastoma

Project description:Background. To develop a radiomics signature for predicting overall survival (OS) and progression-free survival (PFS) in patients with medulloblastoma (MB), and to investigate the incremental prognostic value and underlying biological pathways of the radiomics signature.Methods. A radiomics signature was constructed based on five magnetic resonance (MR) sequences (T1, T1c, T2, FLAIR and ADC) from a training cohort (n = 83) using LASSO-Cox model. Association between the signature and survival was evaluated on a testing cohort (n = 83). Incremental prognostic value of the signature beyond clinicomolecular factors was assessed with respect to calibration, discrimination, reclassification and clinical usefulness by a radiomics-clinicomolecular nomogram. Key pathways associated with the signature were identified. Prognostic value of pathway genes was assessed in a public TCGA cohort.Results. The radiomics signature was significantly associated with OS/PFS, independent from clinicomolecular factors. The radiomics-clinicomolecular nomogram predicted OS (C-index 0.762) and PFS (C-index 0.697) better than either the radiomics signature (C-index: OS: 0.649; PFS: 0.593) or the clinicomolecular nomogram (C-index: OS: 0.725; PFS: 0.691) only, with a better calibration and classification accuracy (net reclassification improvement: OS: 0.298, P = 0.022; PFS: 0.252, P = 0.026). Nine pathways were significantly correlated with the radiomics signature. Average expression value of pathway genes achieved significant risk stratification in public cohort (log-rank P = 0.016). Conclusion. This study demonstrated radiomics signature was an independent prognostic marker and offered incremental value over clinicomolecular factors in OS/PFS predictions for MB patients. The signature was associated with dysregulated pathways affecting patient prognosis in MB.

2020-06-01 | GSE151519 | GEO

Identification of Prognosis-Relevant Subgroups in Patients with Chemoresistant Triple Negative Breast Cancer

Project description:Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study We used gene expression data of TNBC patients with residual disease and different prognosis to molecularly define the clinically relevant subgroups, and developed a 7-gene prognostic signature for chemoresistant TNBCs

2013-01-15 | E-GEOD-43502 | biostudies-arrayexpress

Analyse the differently expressed genes in tamoxifen resistant breast cancer cells

Project description:Tamoxifen resistance has been a major clinical problem and is accountable for relapse in about one third of ER positive breast cancer patients. Most of the recurrent patients will eventually receive chemotherapy. However, the chemosensitivity of these tamoxifen-resistant breast cancer patients has never been explored. In this study, we demonstrate that tamoxifen-resistant breast cancer cells express significantly more BARD1 and BRCA1, which results in the resistance to DNA-damaging chemotherapy including cisplatin and adriamycin , but not to paclitaxel. Silencing BARD1 or BRCA1 expression or inhibition of BRCA1 phosphorylation by Dinaciclib restored the sensitivity to cisplatin in tamoxifen-resistant cells. In addition, we identified that activated PI3K/AKT pathway in tamoxifen-resistant cells was responsible for the upregulation of BARD1 and BRCA1. PI3K inhibitors, BKM120 and BYL719, decreased the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitized them to cisplatin both in vitro and in xenografted mice. Higher BARD1 and BRCA1 expression was associated with poor prognosis of early breast cancer patients, especially the ones received radiotherapy, indicating the potential use of PI3K inhibitors to reverse chemoresistance and radioresistance in ER positive breast cancer patients.

2021-03-15 | GSE111926 | GEO

Expression data from mouse embryonic stem cells

2013-05-03 | GSE44543 | GEO

MicroRNA Expression Analysis of Advanced Colorectal Cancer Reveals a microRNA Signature with Prognostic and Predictive Value

Project description:We performed a prospective cohort study in patients with advanced CRC to identify a miRNA signature that could predict the benefit of receiving first-line chemotherapy for these patients.

2017-12-16 | GSE108153 | GEO

Dual-function of beta-catenin in human tumor hepatocytes

Project description:ß-catenin is part of the cell-cell adhesion complex, where it plays a structural role but is also the key effector of the Wnt pathway, where it is endowed with a transcriptional regulatory activity. Oncogenic mutations of ß-catenin are present in about one third of hepatocellular carcinoma. In most tumors, ß-catenin mutations are heterozygous meaning that mutated and wild-type proteins co-exist in tumor cells. We address here the interplay between wild-type and mutated ß-catenins in liver tumor cells. We have designed a RNA interference strategy in HepG2 cells that allows uncoupling of the two functions of ß-catenin in the same cellular background: nuclear/transcriptional activity, a function almost exclusively mediated by the mutated ß-catenin, and membrane/structural activity, which is mediated by the degradable WT ß-catenin.

2021-01-22 | GSE144107 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data