期刊
GASTROENTEROLOGY
卷 136, 期 4, 页码 1242-1250出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2008.12.048
关键词
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资金
- National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]
- Bennett Family Fund
- Entertainment Industry Foundation National Colorectal Cancer Research Alliance
- Japanese Society for Promotion of Science
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-M 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 cyclo-oxygenase 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.
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