Dataset Information
Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis.
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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.
SUBMITTER: Ogino S
PROVIDER: S-EPMC2663601 | biostudies-literature | 2009 Apr
REPOSITORIES: biostudies-literature
Publications
Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis.
Gastroenterology 20081224 4
<h4>Background & aims</h4>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.<h4>Methods</h4>Among 470 patients with colorectal cancer (stages I-IV) identified in 2 independent prospective cohorts, PPARG expression was ...[more]