ArticleCancers2021
A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer.
Article in Cancers, 2021. 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, 22 citations in OpenAlex.
- Comprehensive analysis ofJournal of thoracic disease · 2026Article
- Recent advances in bladder cancer stem cells (BCSCs): A descriptive review of emerging therapeutic targets.iScience · 2025Review
- Notch2/3-DLL4 interaction in urothelial cancer cell lines supports a tumorigenic role of Notch signaling pathways in bladder carcinoma.PloS one · 2025Article
- Comprehensive analysis of RFC4 as a potential biomarker for regulating the immune microenvironment and predicting immune therapy response in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Analysis of the correlation between RFC4 expression and tumor immune microenvironment and prognosis in patients with cervical cancer.Frontiers in genetics · 2025Article
- Multiomics profiling of urothelial carcinomaiScience · 2024Article
- Exploring the Multiple Roles of Notch1 in Biological Development: An Analysis and Study Based on Phylogenetics and Transcriptomics.International journal of molecular sciences · 2024Article
- Identification of toll-like receptor 5 and acyl-CoA synthetase long chain family member 1 as hub genes are correlated with the severe forms of COVID-19 by Weighted gene co-expression network analysis.IET systems biology · 2023Article
- Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Article
- Clinical Prognostic Implications of Wnt Hub Genes Expression in Medulloblastoma.Cellular and molecular neurobiology · 2023Article
- The oncogenic role of NOTCH1 as biomarker in oral squamous cell carcinoma and oral lichen planus.Dental research journal · 2023Article
- Notch signaling pathway-based classification of bladder cancer in relation to tumor immune infiltration.Central-European journal of immunology · 2023Article
- Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling.International journal of biological sciences · 2022Article
- Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies.Frontiers in pharmacology · 2022Review
- Identification of a naturally-occurring canine model for early detection and intervention research in high grade urothelial carcinoma.Frontiers in oncology · 2022Article
- Construction of miRNA-mRNA network reveals crucial miRNAs and genes in acute myocardial infarction.Journal of biomedical research · 2021Article
- A Comprehensive Bioinformatic Analysis of NOTCH Pathway Involvement in Stomach Adenocarcinoma.Disease markers · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundA hallmark of Notch signaling is its variable role in tumor biology, ranging from tumor-suppressive to oncogenic effects. Until now, the mechanisms and functions of Notch pathways in bladder cancer (BCa) are still unclear.
methodsWe used publicly available data from the GTEx and TCGA-BLCA databases to explore the role of the canonical Notch pathways in BCa on the basis of the RNA expression levels of Notch receptors, ligands, and downstream genes. For statistical analyses of cancer and non-cancerous samples, we used R software packages and public databases/webservers.
resultsWe found differential expression between control and BCa samples for all Notch receptors (NOTCH1, 2, 3, 4), the delta-like Notch ligands (DLL1, 3, 4), and the typical downstream gene hairy and enhancer of split 1 (HES1). NOTCH2/3 and DLL4 can significantly differentiate non-cancerous samples from cancers and were broadly altered in subgroups. High expression levels of NOTCH2/3 receptors correlated with worse overall survival (OS) and shorter disease-free survival (DFS). However, at long-term (>8 years) follow-up, NOTCH2 expression was associated with a better OS and DFS. Furthermore, the cases with the high levels of DLL4 were associated with worse OS but improved DFS. Pathway network analysis revealed that NOTCH2/3 in particular correlated with cell cycle, epithelial-mesenchymal transition (EMT), numbers of lymphocyte subtypes, and modulation of the immune system.
conclusionsNOTCH2/3 and DLL4 are potential drivers of Notch signaling in BCa, indicating that Notch and associated pathways play an essential role in the progression and prognosis of BCa through directly modulating immune cells or through interaction with cell cycle and EMT.
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Registered trials
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 Socratic graph.