Identification of a Notch transcriptomic signature for breast cancer [dataset1]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA984258 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24939000.fastq.gz | Fastqsanger.gz | |||
| SRR24939100.fastq.gz | Fastqsanger.gz | |||
| SRR24939001.fastq.gz | Fastqsanger.gz | |||
| SRR24939101.fastq.gz | Fastqsanger.gz | |||
| SRR24939002.fastq.gz | Fastqsanger.gz |
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Project description:Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would thus be warranted, and in this report, we have established such a classifier. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated and reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by -secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and an optimal 20-gene signature was selected from analysis of the transcriptomes of a broader breast cancer cell line cohort. We validated the signature on two independent patient datasets (METABRIC and Oslo2) and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. Collectively, the 20-gene transcriptional signature has the potential to better stratify patients and to evaluate the response of future Notch-based therapies for breast cancer.
2024-01-05 | GSE235052 | GEO
Project description:Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would thus be warranted, and in this report, we have established such a classifier. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated and reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by -secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and an optimal 20-gene signature was selected from analysis of the transcriptomes of a broader breast cancer cell line cohort. We validated the signature on two independent patient datasets (METABRIC and Oslo2) and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. Collectively, the 20-gene transcriptional signature has the potential to better stratify patients and to evaluate the response of future Notch-based therapies for breast cancer.
2024-01-05 | GSE236749 | GEO
Project description:Identification of a Notch transcriptomic signature for breast cancer
| PRJNA992182 | ENA
Project description:Identification of a Notch transcriptomic signature for breast cancer [dataset2]
| PRJNA992188 | ENA
Project description:BackgroundDysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would be warranted, for example to monitor the effects of future Notch-targeting therapies and to learn whether altered Notch signalling is an off-target effect of current breast cancer therapies. In this report, we have established such a classifier.MethodsTo generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated or reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by γ-secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and a broader breast cancer cell line cohort and sought to validate in independent datasets.ResultsAn optimal 20-gene transcriptomic signature was selected. We validated the signature on two independent patient datasets (METABRIC and Oslo2), and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome.ConclusionsThe 20-gene transcriptional signature will be a valuable tool to evaluate the response of future Notch-targeting therapies for breast cancer, to learn about potential effects on Notch signalling from conventional breast cancer therapies and to better stratify patients for therapy considerations.
| S-EPMC10765899 | biostudies-literature
Project description:A gene expression signature for NOTCH receptor activation
| PRJNA421278 | ENA
Project description:The Notch signalling pathway has been implicated in the development and progression of numerous malignancies, including breast cancer. In breast cancer, the transcriptional programs elicited by Notch activation and the target genes responsible for mediating the downstream effects of the pathway remain poorly understood. Here, we characterise the immediate cellular consequences of Notch activation in breast cancer cells and identify a panel of direct Notch targets with potential relevance in the disease. One key direct transcriptional target of Notch in this context is IER5. Functionally, IER5 activation in breast cancer contributes to the effects of Notch signalling on the self-renewal and proliferative potential of breast cancer stem and progenitor cells. High levels of IER5 mRNA may be an important biomarker indicative of Notch activation in the disease.
2018-01-08 | GSE30288 | GEO
Project description:In many solid cancers and leukemia’s deregulation of the NOTCH signalling pathway is frequently observed, which led to the initiation of clinical trials. However, results from clinical trials using small molecule inhibitors of NOTCH so far are disappointing due to low efficacy and a high toxicity. One shortcoming in these patient studies is the lack of prognostic, predictive and pharmacological biomarkers that could accompany trial design and treatment adaptation. The purpose of this study was to develop an mRNA based NOTCH isoform-specific gene expression signature, which allows for robust identification of NOTCH activity in human tumours.
2019-12-31 | GSE107748 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-05 | GSE236750 | GEO