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 language | English |
|---|---|
| Pages (from-to) | 1138-1147 |
| Number of pages | 10 |
| Journal | International Journal of Cancer |
| Volume | 145 |
| Issue number | 4 |
| Early online date | 2 Mar 2019 |
| DOIs | |
| Publication status | Published - 15 Aug 2019 |
Bibliographical note
© 2019 UICCFunding
Innovate UK, NHS Grampian endowment funds and Vertebrate Antibodies Ltd.
Acknowledgements
The immunohistochemistry was performed with the support of the Grampian Biorepository (www.biorepository.nhsgrampian.org/). The antibodies were developed in collaboration with Vertebrate Antibodies Ltd (www.vertebrateantibodies.com) from whom they are now available commercially.
Keywords
- biomarker
- colorectal cancer
- mitochondria
- prognosis
- uncoupling protein 1
- COLON-CANCER
- STEM-CELLS
- INHIBITION
- UCP1
- ADIPOSE-TISSUE
Access to Document
- Accepted Manuscript
This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at https://doi.org/10.1002/ijc.32198. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.