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

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.

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