Colorectal Cancer Expression of Peroxisome Proliferator-Activated Receptor γ (PPARG, PPARgamma) Is Associated With Good Prognosis

Shuji Ogino, Kaori Shima, Yoshifumi Baba, Katsuhiko Nosho, Natsumi Irahara, Shoko Kure, Liam Lucian Chen, Saori Toyoda, Gregory J. Kirkner, Y. Lynn Wang, Edward L. Giovannucci, Charles S. Fuchs

Research output: Contribution to journalArticle

Abstract

Background & Aims: The peroxisome proliferator-activated receptor γ (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, β-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 Pinteraction > .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.

Original languageEnglish (US)
Pages (from-to)1242-1250
Number of pages9
JournalGastroenterology
Volume136
Issue number4
DOIs
Publication statusPublished - Apr 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Gastroenterology

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