ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Prognostic significance of TRAIL signaling molecules in stage II and III colorectal cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. 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, 76 citations in OpenAlex.
- The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.British journal of cancer · 2011Trial
- Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer.Cell reports. Medicine · 2025Article
- EX527, a sirtuins 1 inhibitor, sensitizes T-cell leukemia to death receptor-mediated apoptosis by downregulating cellular FLICE inhibitory protein.Cancer biology & therapy · 2024Article
- A Four-Gene Autophagy-Related Prognostic Model Signature and Its Association With Immune Phenotype in Lung Squamous Cell Carcinoma.Cancer reports (Hoboken, N.J.) · 2024Article
- TRAIL C1595T Variant Critically Alters the Level of sTRAIL in Terms of Histopathological Parameters in Colorectal Cancer.Indian journal of clinical biochemistry : IJCB · 2024Article
- Restoring TRAILR2/DR5-Mediated Activation of Apoptosis upon Endoplasmic Reticulum Stress as a Therapeutic Strategy in Cancer.International journal of molecular sciences · 2022Review
- Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.Viruses · 2022Review
- cFLIP downregulation is an early event required for endoplasmic reticulum stress-induced apoptosis in tumor cells.Cell death & disease · 2022Article
- TRAIL signaling promotes entosis in colorectal cancer.The Journal of cell biology · 2021Article
- PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells.International journal of molecular sciences · 2021Article
- TRAIL of Hope Meeting Resistance in Cancer.Trends in cancer · 2020Review
- Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids.Cell death and differentiation · 2020Article
- Genomically informed small-molecule drugs overcome resistance to a sustained-release formulation of an engineered death receptor agonist in patient-derived tumor models.Science advances · 2019Article
- The arginine methyltransferase PRMT5 and PRMT1 distinctly regulate the degradation of anti-apoptotic protein CFLARJournal of experimental & clinical cancer research : CR · 2019Article
- c-FLIP, a Novel Biomarker for Cancer Prognosis, Immunosuppression, Alzheimer's Disease, Chronic Obstructive Pulmonary Disease (COPD), and a Rationale Therapeutic Target.Biomarkers journal · 2019Article
- Recent advances in targeted therapy of colorectal cancer: impacts of monoclonal antibodies nanoconjugates.BioImpacts : BI · 2019Article
- Telomerase reverse transcriptase interference synergistically promotes tumor necrosis factor‑related apoptosis‑inducing ligand‑induced oral squamous cell carcinoma apoptosis and suppresses proliferation in vitro and in vivo.International journal of molecular medicine · 2018Article
- Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress.Cellular & molecular biology letters · 2018Article
- IHC-based subcellular quantification provides new insights into prognostic relevance of FLIP and procaspase-8 in non-small-cell lung cancer.Cell death discovery · 2017Article
- Death receptor 5 (DR5) and a 5-gene apoptotic biomarker panel with significant differential diagnostic potential in colorectal cancer.Scientific reports · 2016Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability and chemotherapy-induced apoptosis in colorectal cancer. In this study, we determined the prognostic significance of c-FLIP, caspase 8, TRAIL and DR5 expression in tissues from patients with stage II and III colorectal cancer. EXPERIMENTAL
designTissue microarrays were constructed from matched normal and tumor tissue derived from patients (n = 253) enrolled in a phase III trial of adjuvant 5-fluorouracil-based chemotherapy versus postoperative observation alone. TRAIL, DR5, caspase 8, and c-FLIP expression levels were determined by immunohistochemistry.
resultsColorectal tumors displayed significantly higher expression levels of c-FLIP (P < 0.001), caspase 8 (P = 0.01), and DR5 (P < 0.001), but lower levels of TRAIL (P < 0.001) compared with matched normal tissue. In univariate analysis, higher TRAIL expression in the tumor was associated with worse overall survival (P = 0.026), with a trend to decreased relapse-free survival (RFS; P = 0.06), and higher tumor c-FLIP expression was associated with a significantly decreased RFS (P = 0.015). Using multivariate predictive modeling for RFS in all patients and including all biomarkers, age, treatment, and stage, we found that the model was significant when the mean tumor c-FLIP expression score and disease stage were included (P < 0.001). As regards overall survival, the overall model was predictive when both TRAIL expression and disease stage were included (P < 0.001).
conclusionsHigh c-FLIP and TRAIL expression may be independent adverse prognostic markers in stage II and III colorectal cancer and might identify patients most at risk of relapse.
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