Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis.
Gastroenterology
; 136(4): 1242-50, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19186181
ABSTRACT
BACKGROUND & AIMS:
The peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. There is controversy over the pro-oncogenic or antioncogenic effects of PPARG, and little is known about its prognostic significance in colon cancer.METHODS:
Among 470 patients with colorectal cancer (stages I-IV) identified in 2 independent prospective cohorts, PPARG expression was detected in 102 tumors (22%) by immunohistochemistry. Cox proportional hazards models were used to compute hazard ratios (HRs) of colorectal cancer-specific and overall mortalities, adjusted for patient characteristics and molecular features including cyclooxygenase 2, fatty acid synthase, KRAS, BRAF, PIK3CA, p53, p21, beta-catenin, LINE-1 hypomethylation, microsatellite instability (MSI), and the CpG island methylation phenotype (CIMP).RESULTS:
Compared with patients with PPARG-negative tumors, patients with PPARG-positive tumors had significantly lower overall mortality, determined by Kaplan-Meier analysis (P=.0047), univariate Cox regression (HR, 0.55; 95% confidence interval [CI], 0.37-0.84; P=.0053), and multivariate analysis (adjusted HR, 0.43; 95% CI, 0.27-0.69; P=.0004). Patients with PPARG-positive tumors experienced lower colorectal cancer-specific mortality (adjusted HR, 0.44; 95% CI, 0.25-0.79; P=.0054). The relationship between PPARG and lower mortality did not appear to be significantly modified by MSI, CIMP, LINE-1, or the other clinical and molecular variables examined (all P(interaction)>.05).CONCLUSIONS:
Tumor expression of PPARG is independently associated with longer survival of patients. PPARG expression appears to mark an indolent subset of colorectal cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Biomarcadores Tumorais
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PPAR gama
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Gastroenterology
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos