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

Abdo Alnabulsi, Beatriz Cash, Yehfang Hu, Linda Silina, Ayham Alnabulsi, Graeme I. Murray (Corresponding Author)

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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.
Original languageEnglish
Pages (from-to)1138-1147
Number of pages10
JournalInternational Journal of Cancer
Volume145
Issue number4
Early online date2 Mar 2019
DOIs
Publication statusPublished - 15 Aug 2019

Keywords

  • biomarker
  • colorectal cancer
  • mitochondria
  • prognosis
  • uncoupling protein 1
  • COLON-CANCER
  • STEM-CELLS
  • INHIBITION
  • UCP1
  • ADIPOSE-TISSUE

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