The expression of brown fat-associated proteins in colorectal cancer and the relationship of uncoupling protein 1 with prognosis.

Abstract

Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer related death. The aberrant expression of a brown fat-like phenotype in cancer cells has been previously implicated in tumour growth. Therefore, the expression of brown fat-associated proteins in colorectal cancer could be associated with tumour prognosis. Monoclonal antibodies to brown fat-associated proteins CIDEA, ELOVL3, ELOVL5, and UCP1 were developed. The antibodies were used to profile the expression of protein targets by immunohistochemistry in a discovery cohort comprising 50 normal colonic mucosa samples and 274 primary colorectal cancers and a validation cohort comprising 549 colorectal cancers. Immunostaining for UCP1 was observed in the majority of colorectal tumours while no immunostaining was observed in normal colonic mucosa (p < 0.001). The expression of UCP1 was significantly associated with better overall survival in both the discovery cohort (HR = 0.615, 95%CI = 0.416-0.909, χ2 = 6.119, p = 0.013) and the validation cohort (HR = 0.629, 95%CI = 0.480-0.825, χ2 = 11.558, p = 0.001). Furthermore, UCP1 was independently prognostic in multivariate analysis (p = 0.004). This study has identified the brown fat-like phenotype as a novel pathway associated with survival in colorectal cancer. The expression of UCP1 was identified as a significant prognostic biomarker for colorectal cancer.