ArticleBMC medicine2021
Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy.
Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- Article
- Identification of SLIT3 mutation as a response biomarker for immune checkpoint inhibitor therapy in non-small cell lung cancer.Discover oncology · 2026Article
- The dual role of the Notch signaling pathway in digestive system cancers.European journal of medical research · 2026Review
- A 10-pathway burden score complements tumor mutational burden for outcome stratification in non-small cell lung cancer.Frontiers in medicine · 2026Article
- An emerging targeted strategy for gastric cancer: the multi-pathway regulatory potential of Chinese medicine monomers.Frontiers in oncology · 2026Review
- Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy.Translational lung cancer research · 2025Review
- Bladder Cancer: Uncovering the Predictive Role of NOTCH as an Emerging Candidate Biomarker for Therapeutic Strategies.Cancers · 2025Review
- Predicting response and survival of lung adenocarcinoma under anti-programmed death-1 therapy using biological deep learning.Briefings in bioinformatics · 2025Article
- Integrated singlecell and bulk RNA-seq analysis identifies a prognostic signature related to inflammation in colorectal cancer.Scientific reports · 2025Article
- Global trends and emerging insights in BRAF and MEK inhibitor resistance in melanoma: a bibliometric analysis.Frontiers in molecular biosciences · 2025Article
- Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization.Frontiers in oncology · 2025Article
- Integrated Multi-Omics Approaches for Predicting Immune Checkpoint Inhibitor Response in NSCLC - Insights From Genomics, Proteomics, and Metabolomics.Lung Cancer (Auckland, N.Z.) · 2025Review
- Deep learning to estimate response of concurrent chemoradiotherapy in non-small-cell lung carcinoma.Journal of translational medicine · 2024Article
- Large-scale whole-exome sequencing analyses identified protein-coding variants associated with immune-mediated diseases in 350,770 adults.Nature communications · 2024Article
- Mutational variant allele frequency profile as a biomarker of response to immune checkpoint blockade in non-small cell lung Cancer.Journal of translational medicine · 2024Article
- Signaling pathways in colorectal cancer implications for the target therapies.Molecular biomedicine · 2024Review
- Deep Learning Based on Computed Tomography Predicts Response to Chemoimmunotherapy in Lung Squamous Cell Carcinoma.Aging and disease · 2024Article
- GRIN2A mutation is a novel indicator of stratifying beneficiaries of immune checkpoint inhibitors in multiple cancers.Cancer gene therapy · 2024Article
- Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.BMC medicine · 2024Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy.
methodsWe tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data.
resultsWe collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets.
conclusionsOur findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.
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