ArticleCancers2020
A Molecular Test for Quantifying Functional Notch Signaling Pathway Activity in Human Cancer.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Pathological and therapeutic implications of Notch overexpression in claudin-low breast cancers.Human cell · 2026Article
- Quantification of Signal Transduction Pathway Activity in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2025Article
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- RNA sequencing reveals transcriptional signatures of drug response and SARS-CoV-2 interaction in colorectal cancer cells.Frontiers in medicine · 2025Article
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- Quantitative characterization of immune cells by measuring cellular signal transduction pathway activity.Scientific reports · 2024Article
- IncreasedInternational journal of molecular sciences · 2024Article
- Machine learning developed a CD8Scientific reports · 2024Article
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- Study Deciphering the Crucial Involvement of Notch Signaling Pathway in Human Cancers.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Machine Learning Developed a Programmed Cell Death Signature for Predicting Prognosis, Ecosystem, and Drug Sensitivity in Ovarian Cancer.Analytical cellular pathology (Amsterdam) · 2023Article
- A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture.Cancer research · 2022Article
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- Improved diagnosis of inflammatory bowel disease and prediction and monitoring of response to anti-TNF alpha treatment based on measurement of signal transduction pathway activity.Frontiers in pharmacology · 2022Article
- Review
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- Insights into the Role of Oxidative Stress in Ovarian Cancer.Oxidative medicine and cellular longevity · 2021Review
- Androgen Receptor Pathway Activity Assay for Sepsis Diagnosis and Prediction of Favorable Prognosis.Frontiers in medicine · 2021Article
- RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies.Frontiers in genetics · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe Notch signal transduction pathway is pivotal for various physiological processes, including immune responses, and has been implicated in the pathogenesis of many diseases. The effectiveness of various targeted Notch pathway inhibitors may vary due to variabilities in Notch pathway activity among individual patients. The quantitative measurement of Notch pathway activity is therefore essential to identify patients who could benefit from targeted treatment.
methodsWe here describe a new assay that infers a quantitative Notch pathway activity score from the mRNA levels of generally conserved direct NOTCH target genes. Following the calibration and biological validation of our Notch pathway activity model over a wide spectrum of human cancer types, we assessed Notch pathway activity in a cohort of T-ALL patient samples and related it to biological and clinical parameters, including outcome.
resultsWe developed an assay using 18 select direct target genes and high-grade serous ovarian cancer for calibration. For validation, seven independent human datasets (mostly cancer series) were used to quantify Notch activity in agreement with expectations. For T-ALL, the median Notch pathway activity was highest for samples with strong NOTCH1-activating mutations, and T-ALL patients of the TLX subtype generally had the highest levels of Notch pathway activity. We observed a significant relationship between ICN1 levels and the absence/presence of NOTCH1-activating mutations with Notch pathway activity scores. Patients with the lowest Notch activity scores had the shortest event-free survival compared to other patients.
conclusionsHigh Notch pathway activity was not limited to T-ALL samples harboring strong NOTCH1 mutations, including juxtamembrane domain mutations or hetero-dimerization combined with PEST-domain or FBXW7 mutations, indicating that additional mechanisms may activate Notch signaling. The measured Notch pathway activity was related to intracellular NOTCH levels, indicating that the pathway activity score more accurately reflects Notch pathway activity than when it is predicted on the basis of NOTCH1 mutations. Importantly, patients with low Notch pathway activity had a significantly shorter event-free survival compared to patients showing higher activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.