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Prognostic Significance of TRAIL Signaling Molecules in Stage II and III Colorectal Cancer
- Source :
- Clinical Cancer Research. 16:3442-3451
- Publication Year :
- 2010
- Publisher :
- American Association for Cancer Research (AACR), 2010.
-
Abstract
- Purpose: We 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 Design: Tissue 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.Results: Colorectal 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).Conclusions: High 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. Clin Cancer Res; 16(13); 3442–51. ©2010 AACR.
- Subjects :
- Adult
Male
Oncology
Cancer Research
Pathology
medicine.medical_specialty
Colorectal cancer
Eukaryotic Initiation Factor-3
medicine.medical_treatment
CASP8 and FADD-Like Apoptosis Regulating Protein
Caspase 8
Article
TNF-Related Apoptosis-Inducing Ligand
Internal medicine
Humans
Medicine
Aged
Randomized Controlled Trials as Topic
Aged, 80 and over
Chemotherapy
Tissue microarray
business.industry
Cancer
Middle Aged
Prognosis
medicine.disease
Receptors, TNF-Related Apoptosis-Inducing Ligand
Cytokine
Clinical Trials, Phase III as Topic
Chemotherapy, Adjuvant
Immunohistochemistry
Female
Tumor necrosis factor alpha
Colorectal Neoplasms
business
Signal Transduction
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....39220bb9a2af974761c52b8ffd4e9ef7