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    GENE:

    NOTCH4 (Notch 4)

    i
    Other names: NOTCH4, INT3, Neurogenic Locus Notch Homolog Protein 4, Notch Homolog 4
    27d
    FOXM1 influences DNA methylation to augment TACC3 alternative splicing directed by KAT2A in hepatocellular carcinoma. (PubMed, Clin Mol Hepatol)
    Thus, FOXM1 reshapes the TACC3-KAT2A interaction, while DNMT1 drives context-dependent DNA methylation, activating the CDK1-inhibitory kinase PKMYT1. We uncovered TACC3-KAT2A as an emerging regulatory axis caused by alternative splicing in HCC and propose FOXM1-driven TACC3 inhibition to synergistically disrupt mitotic fidelity and transcriptional regulation, potentially offering new therapeutic avenues for HCC with reduced toxicity to the normal liver.
    Journal
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    TACC3 (Transforming acidic coiled-coil containing protein 3) • NOTCH4 (Notch 4) • DNMT1 (DNA methyltransferase 1) • FOXM1 (Forkhead Box M1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    1m
    Designing a Multi-Epitope Vaccine Against NOTCH1 and NOTCH4: A Computational Approach for Triple-Negative Breast Cancer. (PubMed, Biomed Res Int)
    Molecular dynamics simulations (repeated three times) showed that the vaccine and its complexes with MHC I, MHC II, and TLR4 are stable, with the docked complexes exhibiting dynamic interaction. These findings collectively highlight a targeted approach to combating TNBC, demonstrating the vaccine's potential as a therapeutic candidate.
    Journal
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    NOTCH1 (Notch 1) • NOTCH4 (Notch 4) • TLR4 (Toll Like Receptor 4) • TLR7 (Toll Like Receptor 7)
    1m
    Genomic Profiling of Highly Aggressive Musculoskeletal Sarcomas Identifies Potential Therapeutic Targets: A Single-Center Experience. (PubMed, Cancers (Basel))
    Early access to genomic analyses, routine germline assessment, and broad gene panels would help in identifying possible targeted drugs with sufficient evidence of activity beneficial to each patient. In the clinical management of advanced sarcoma patients, when analyzing cost-effectiveness and sustainability, the role of the Molecular Tumor Board in the governance of the complexity introduced by mutational oncology should be considered.
    Journal
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    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PMS2 (PMS1 protein homolog 2) • MUC16 (Mucin 16, Cell Surface Associated) • NOTCH4 (Notch 4) • RHOA (Ras homolog family member A) • BARD1 (BRCA1 Associated RING Domain 1) • CCND3 (Cyclin D3) • DDR2 (Discoidin domain receptor 2) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)
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    Archer® VariantPlex® Solid Tumor Kit
    2ms
    Subtype-Independent Dysregulation of the Notch Signaling Pathway and Its miRNA Regulators in Breast Cancer. (PubMed, Biomedicines)
    The consistent alterations suggest the presence of a shared Notch-driven oncogenic signature in breast cancer, potentially driving cell proliferation, stemness, and resistance to therapy. These findings enhance our understanding of Notch signaling in breast cancer and propose novel miRNA-Notch interactions as candidate targets for therapeutic intervention.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • MIR155 (MicroRNA 155) • NOTCH4 (Notch 4) • APH1A (Aph-1 Homolog A, Gamma-Secretase Subunit) • CTBP1 (C-Terminal Binding Protein 1) • MIR381 (MicroRNA 381) • TLE2 (TLE Family Member 2, Transcriptional Corepressor) • HEY1 (Hes Related Family BHLH Transcription Factor With YRPW Motif 1) • MIR145 (MicroRNA 145) • MIR98 (MicroRNA 98) • TLE4 (TLE Family Member 4 Transcriptional Corepressor)
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    HER-2 positive • HER-2 negative
    3ms
    Investigation of Transcriptome and Kinome in Non Metastatic and Metastatic Renal Clear Cancer Stem Cells and Their Relationship with Gut Microbiota. (PubMed, Mol Biotechnol)
    Also, the Actinobacteria and Gammaproteobacteria possible role in renal cancer development via relation to cancer stem cells. The gut microbiota and its components were considered for their possible relevance in the development of RCC.
    Journal • IO biomarker
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    NOTCH4 (Notch 4)
    3ms
    Dynamic tumor microenvironment remodeling from laryngeal leukoplakia to carcinoma revealed by single-cell transcriptomics. (PubMed, Gene)
    We also observed the progressive activation of genes involved in redox processes (NQO1, GSTM3, UCHL1, NTRK2) via the KEAP1-NRF2 pathway. This work systematically characterizes the cellular and molecular landscape during laryngeal leukoplakia malignant transformation, providing a framework for future mechanistic studies and early detection strategies.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • GSTP1 (Glutathione S-transferase pi 1) • NOTCH4 (Notch 4) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • JAG1 (Jagged Canonical Notch Ligand 1)
    5ms
    Study on the possible mechanism of Shoutai pill in the treatment of unexplained recurrent abortion. (PubMed, Afr J Reprod Health)
    These findings suggest that Shoutai Pill exerts a protective effect by modulating immune responses, enhancing antiviral defense, and maintaining decidual cell stability. This multi-tiered approach provides mechanistic evidence supporting the clinical potential of Shoutai Pill as an adjunct therapy for unexplained recurrent abortion.
    Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • NOTCH4 (Notch 4)
    5ms
    Role of Notch gene receptors as prognostic biomarkers in colorectal cancer. (PubMed, Sci Rep)
    Notch receptor polymorphism, especially Notch3, is associated with increased protein expression and a higher risk of having CRC. Furthermore, poor survival in patients with Notch3 and Notch4 polymorphism suggests their potential as prognostic biomarker in CRC.
    Journal
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    NOTCH1 (Notch 1) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3) • NOTCH4 (Notch 4)
    5ms
    Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types. (PubMed, Cancer Res Commun)
    In contrast, mutation and methylation patterns in ovarian mucinous carcinomas were different from gastrointestinal mucinous carcinomas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.
    Journal
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    ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • JAK1 (Janus Kinase 1) • RAD51C (RAD51 paralog C) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • NOTCH4 (Notch 4)
    6ms
    Molecular impact of NOTCH signaling dysregulation on ovarian cancer progression, chemoresistance, and taxane response. (PubMed, Biomed Pharmacother)
    In the resistant in vitro cell line model, significant upregulation of NOTCH signaling pathway, namely NOTCH3, was observed after treatment with experimental Stony Brook taxanes (SB-Ts), with high efficacy against paclitaxel-resistant ovarian tumor cells...Based on our results, we suggest the NOTCH3 gene as a potential target for preclinical studies on resistant ovarian tumors. The current study also highlights the NOTCH4 gene as a potential predictive biomarker of therapeutic response in ovarian cancer.
    Journal
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    NOTCH1 (Notch 1) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3) • NOTCH4 (Notch 4)
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    paclitaxel
    6ms
    HLA-DOB: A Key "Coordinator" Between Cutaneous Melanoma and Psoriasis. (PubMed, J Cancer)
    Our findings suggest an inverse causal relationship between melanoma and psoriasis. Importantly, we also found that HLA-DOB can be served as a key "coordinator" between cutaneous melanoma and psoriasis: a risk gene of psoriasis and a protective factor of cutaneous melanoma.
    Journal
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    NOTCH4 (Notch 4)
    6ms
    Cemento-osseous dysplasia with a NOTCH4 mutation: a case report. (PubMed, Virchows Arch)
    This finding expands the spectrum of genetic alterations associated with COD and raises the possibility of Notch signaling involvement in its pathogenesis. Incorporating molecular profiling into the diagnostic workflow may improve discrimination between COD and COF and deepen our understanding of fibro-osseous lesions of the jaw.
    Journal
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    NOTCH4 (Notch 4)
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    RAS mutation
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    TruSight Oncology 500 Assay