Overexpression of FLIPL Is an Independent Marker of Poor Prognosis in Colorectal Cancer Patients

Overexpression of FLIPL Is an Independent Marker of Poor Prognosis in Colorectal Cancer Patients

Purpose: Colorectal cancer is one of the most common cancers. The tumor necrosis factor–related apoptosis inducing ligand (TRAIL) pathway transmits apoptotic signals and anticancer agents that activate this system, which are in clinical development. We sought to determine the prognostic value of the...

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Bibliographic Details
Published in:Clinical cancer research Vol. 13; no. 17; pp. 5070 - 5075
Main Authors: ULLENHAG, Gustave J, MUKHERJEE, Abhik, WATSON, Nicholas F. S, AL-ATTAR, Ahmad H, SCHOLEFIELD, John H, DURRANT, Lindy G
Format: Journal Article
Language:English
Published: Philadelphia, PA American Association for Cancer Research 01-09-2007
Subjects:
Aged
Aged, 80 and over
Antineoplastic agents
Biological and medical sciences
Biomarkers, Tumor - analysis
CASP8 and FADD-Like Apoptosis Regulating Protein - analysis
CASP8 and FADD-Like Apoptosis Regulating Protein - physiology
Colorectal Cancer
Colorectal Neoplasms - chemistry
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Female
FLIP
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Male
Medical sciences
Middle Aged
Multivariate Analysis
Pharmacology. Drug treatments
Prognosis
Prognostic Factor
Receptors, TNF-Related Apoptosis-Inducing Ligand - analysis
Receptors, Tumor Necrosis Factor - analysis
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tissue Microarray
TRAIL-R1
TRAIL-R2
Tumors
Colonic disease
Human
Rectal disease
Prognosis
Colorectal cancer
Biological marker
Gene overexpression
Digestive diseases
Intestinal disease
Malignant tumor
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Summary:Purpose: Colorectal cancer is one of the most common cancers. The tumor necrosis factor–related apoptosis inducing ligand (TRAIL) pathway transmits apoptotic signals and anticancer agents that activate this system, which are in clinical development. We sought to determine the prognostic value of the clinically most relevant members of this pathway in colorectal cancer patients. Experimental Design: We used an arrayed panel of colorectal cancer tissue to assess the protein expression of the functional TRAIL receptors (TRAIL-R1 and TRAIL-R2) and both the long and short forms of FLICE inhibitory protein (FLIP L and FLIP S ). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by Cox multivariate analysis. Results: The TRAIL receptors and FLIP S were not associated with survival. On univariate analysis, strong FLIP L expression was associated with a significantly higher survival ( P = 0.0082). On multivariate analysis using the Cox proportional hazards model, FLIP L phenotype was significantly associated with a poor prognosis in this series (hazard ratio, 2.04; 95% confidence interval, 1.18-3.56; P = 0.011). Conclusions: Overexpression of FLIP L , but not TRAIL-R1 or TRAIL-R2, provides stage-independent prognostic information in colorectal cancer patients. This may indicate a clinically more aggressive phenotype and a subset of patients for whom more extensive adjuvant treatment would be appropriate.
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ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-06-2547