ArticleBreast cancer research : BCR2024
Identification of a Notch transcriptomic signature for breast cancer.
Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 7 citations in OpenAlex.
- Subclassification of Small Cell Lung Cancer Based on Gene Expression Signatures and Machine Learning.Cancer research communications · 2026Article
- Human-specific genomic evolution of a regulatory network enables fine-tuning of N-cadherin gene expression.Cellular and molecular life sciences : CMLS · 2025Article
- Molecular Basis of Breast Tumor Heterogeneity.Advances in experimental medicine and biology · 2025Review
- Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies.Biomolecules · 2024Review
- Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple-negative breast cancer.EMBO molecular medicine · 2024Article
- IncreasedInternational journal of molecular sciences · 2024Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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