ArticleBritish journal of cancer2009
Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer.
Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Prognostic value and clinicopathological differences of HIFs in colorectal cancer: evidence from meta-analysis.PloS one · 2013Pooled it
- Notch signaling in the tumor immune microenvironment of colorectal cancer: mechanisms and therapeutic opportunities.Journal of translational medicine · 2025Review
- The Prediction of DLL4 as a Prognostic Biomarker in Patients with Gastric Cancer Using Anti-DLL4 Nanobody.Journal of gastrointestinal cancer · 2024Article
- Delta-like ligand 4 level in colorectal cancer is associated with tumor aggressiveness and clinical outcome.Cancer biomarkers : section A of Disease markers · 2022Article
- Prognostic Index for Nonsmall Cell Lung Cancer Based on Immune-Related Genes Expression.BioMed research international · 2022Article
- Prognostic value of HIF-1α in digestive system malignancies: evidence from a systematic review and meta-analysis.Gastroenterology and hepatology from bed to bench · 2022Article
- Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors.Molecular cancer therapeutics · 2021Article
- Article
- Increased Expression of Delta-like Ligand 4 in Mycosis Fungoides.Acta dermato-venereologica · 2020Article
- Inflammation-induced colon cancer in uPA-deficient mice is associated with a deregulated expression of Notch signaling pathway components.Molecular and cellular biochemistry · 2020Article
- The PERK Branch of the Unfolded Protein Response Promotes DLL4 Expression by Activating an Alternative Translation Mechanism.Cancers · 2019Article
- High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.Journal of Cancer · 2019Article
- Tumor suppressive effects of the pleiotropically acting miR-195 in colorectal cancer cells.EXCLI journal · 2019Article
- Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis.Frontiers in oncology · 2018Article
- Article
- Article
- Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.BMC cancer · 2017Article
- Role of Delta-Notch signaling in cerebral cavernous malformations.Neurosurgical review · 2016Review
- The effect of epigenetic silencing and TP53 mutation on the expression of DLL4 in human cancer stem disorder.Oncotarget · 2016Article
- Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth.Molecular cancer therapeutics · 2016Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundDelta-like ligand 4 (Dll4) is a Notch ligand that is upregulated by hypoxia and vascular endothelial growth factor-A (VEGF-A) and is reported to have a role in tumor angiogenesis. Evidence from xenograft studies suggests that inhibiting Dll4-Notch signalling may overcome resistance to anti-VEGF therapy. The aim of this study was to characterise the expression of Dll4 in colon cancer and to assess whether it is associated with markers of hypoxia and prognosis.
methodIn all, 177 colon cancers were represented in tissue microarrays. Immunohistochemistry was performed using validated antibodies against Dll4, VEGF, hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and carbonic anhydrase 9 (CA9).
resultsThe expression of Dll4 was observed preferentially in the endothelium of 71% (125 out of 175) of colon cancers, but not in the endothelium adjacent to normal mucosa (none out of 107, P<0.0001). The expression of VEGF was significantly associated with HIF-2alpha (P<0.0001) and Dll4 (P=0.010). Only HIF-2alpha had a significant multivariate prognostic effect (hazard ratio 1.61, 95% confidence interval 1.01-2.57). Delta-like ligand 4 was also expressed by neoplastic cells, particularly neoplastic goblet cells.
conclusionEndothelial expression of Dll4 is not a prognostic factor, but is significantly associated with VEGF. Assessing endothelial Dll4 expression may be critical in predicting response to anti-VEGF therapies.
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