Clinical Significance of Peroxisome Proliferator-Activated Receptor Γ and MED1/TRAP220 in Patients with Operable Colorectal Cancer

Background: The peroxisome proliferator-activated receptor γ (PPAR gamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Med1/TRAP220 is an essential component of the TRAP/Mediator complex. However, no published data are available concerning the biological and clinical significance of PPARγ and TRAP220 in colorectal cancer (CRC). The objective of this study was to clarify whether the PPARγ or TRAP220 are significant prognostic marker in resectable colorectal cancer (CRC). Methods: Between May 2005 and December 2008, 399 patients who underwent curative resection for CRC were enrolled in this study. We investigated the presence of PPARγ and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. The correlation between the expression of these factors and clinicopathologic features was investigated. The 5-year disease-free survival (DFS) and overall survival (OS) of patients with tumors expressing different levels of PPARγ and TRAP220 were evaluated by the Kaplan-Meier method. Results: Median age of the patients was 63 years (range 22-87 years), and median follow up duration 61.1 months (range 2-114 months). PPARγ and TRAP220 expression was correlated significantly with depth of invasion (p = 0.013, p = 0.001, respectively). Expression of TRAP220 was also related to lymph node metastasis and TNM stage (p = 0.001, respectively). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-yr DFS (p = 0.051). Patients who were PPARγ positive combined with TRAP220 positive had a better 5- yr DFS (64.8% vs 79.3%, p = 0.013). The expressions of both PPARγ and TRAP220 significantly affected DFS on multivariate analysis (HR = 0.620, 95% CI, 0.379-0.997; p = 0.048). Conclusions: Based on our results, TRAP220 may be valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARγ and TRAP220 represent a biomarker for good prognosis in CRC patients.