Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis.
OBJECTIVE
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.
Ogino
Shuji
S
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, and Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. shuji_ogino@dfci.harvard.edu
Shima
Kaori
K
Baba
Yoshifumi
Y
Nosho
Katsuhiko
K
Irahara
Natsumi
N
Kure
Shoko
S
Chen
Li
L
Toyoda
Saori
S
Kirkner
Gregory J
GJ
Wang
Y Lynn
YL
Giovannucci
Edward L
EL
Fuchs
Charles S
CS
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047495:PPAR gamma / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; D047495:PPAR gamma