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)

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Brown Adipose Tissue
Colorectal Neoplasms
Proteins
Neoplasms
Mucous Membrane
Phenotype
Uncoupling Protein 1
Multivariate Analysis
Biomarkers
Immunohistochemistry
Monoclonal Antibodies
Antibodies
Growth

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{c8653dcf42c14160bd4745b3adc558b6,
title = "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.",
keywords = "biomarker, colorectal cancer, mitochondria, prognosis, uncoupling protein 1, COLON-CANCER, STEM-CELLS, INHIBITION, UCP1, ADIPOSE-TISSUE",
author = "Abdo Alnabulsi and Beatriz Cash and Yehfang Hu and Linda Silina and Ayham Alnabulsi and Murray, {Graeme I.}",
note = "{\circledC} 2019 UICC Funding 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.",
year = "2019",
month = "8",
day = "15",
doi = "10.1002/ijc.32198",
language = "English",
volume = "145",
pages = "1138--1147",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - The expression of brown fat associated proteins in colorectal cancer and the relationship of uncoupling protein 1 with prognosis

AU - Alnabulsi, Abdo

AU - Cash, Beatriz

AU - Hu, Yehfang

AU - Silina, Linda

AU - Alnabulsi, Ayham

AU - Murray, Graeme I.

N1 - © 2019 UICC Funding 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.

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

KW - biomarker

KW - colorectal cancer

KW - mitochondria

KW - prognosis

KW - uncoupling protein 1

KW - COLON-CANCER

KW - STEM-CELLS

KW - INHIBITION

KW - UCP1

KW - ADIPOSE-TISSUE

UR - http://www.scopus.com/inward/record.url?scp=85062495561&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/expression-brown-fatassociated-proteins-colorectal-cancer-relationship-uncoupling-protein-1-prognosi

U2 - 10.1002/ijc.32198

DO - 10.1002/ijc.32198

M3 - Article

VL - 145

SP - 1138

EP - 1147

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -