The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance

Abdo Alnabulsi, Rebecca Swan, Beatriz Cash, Ayham Alnabulsi, Graeme I. Murray*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Citations (Scopus)
4 Downloads (Pure)

Abstract

Background:
Colorectal cancer is a common malignancy and one of the leading causes of cancer-related deaths. The metabolism of omega fatty acids has been implicated in tumour growth and metastasis.

Methods:
This study has characterised the expression of omega fatty acid metabolising enzymes CYP4A11, CYP4F11, CYP4V2 and CYP4Z1 using monoclonal antibodies we have developed. Immunohistochemistry was performed on a tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosa.

Results:
The differential expression of CYP4A11 and CYP4F11 showed a strong association with survival in both the whole patient cohort (hazard ratio (HR)=1.203, 95% CI=1.092–1.324, χ2=14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95% CI=1.095–1.488, χ2=9.988, P=0.007). Multivariate analysis revealed that the differential expression of CYP4A11 and CYP4F11 was independently prognostic in both the whole patient cohort (P=0.019) and in mismatch repair proficient tumours (P=0.046).

Conclusions:
A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours.
Original languageEnglish
Pages (from-to)1612-1620
Number of pages9
JournalBritish Journal of Cancer
Volume116
Issue number12
DOIs
Publication statusPublished - 6 Jun 2017

Keywords

  • biomarker
  • colorectal cancer
  • cytochrome P450
  • omega fatty acid
  • prognosis
  • BREAST-CANCER
  • MICROSATELLITE INSTABILITY
  • MATRIX METALLOPROTEINASES
  • HUMAN CYTOCHROME-P450
  • CELL-PROLIFERATION
  • PROSTATE-CANCER
  • COLON-CANCER
  • METASTASIS
  • INHIBITORS
  • GROWTH

Cite this

@article{b377362eea1e460a86232fc36e2f2ba9,
title = "The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance",
abstract = "Background:Colorectal cancer is a common malignancy and one of the leading causes of cancer-related deaths. The metabolism of omega fatty acids has been implicated in tumour growth and metastasis.Methods:This study has characterised the expression of omega fatty acid metabolising enzymes CYP4A11, CYP4F11, CYP4V2 and CYP4Z1 using monoclonal antibodies we have developed. Immunohistochemistry was performed on a tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosa.Results:The differential expression of CYP4A11 and CYP4F11 showed a strong association with survival in both the whole patient cohort (hazard ratio (HR)=1.203, 95{\%} CI=1.092–1.324, χ2=14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95{\%} CI=1.095–1.488, χ2=9.988, P=0.007). Multivariate analysis revealed that the differential expression of CYP4A11 and CYP4F11 was independently prognostic in both the whole patient cohort (P=0.019) and in mismatch repair proficient tumours (P=0.046).Conclusions:A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours.",
keywords = "biomarker, colorectal cancer, cytochrome P450, omega fatty acid, prognosis, BREAST-CANCER, MICROSATELLITE INSTABILITY, MATRIX METALLOPROTEINASES, HUMAN CYTOCHROME-P450, CELL-PROLIFERATION, PROSTATE-CANCER, COLON-CANCER, METASTASIS, INHIBITORS, GROWTH",
author = "Abdo Alnabulsi and Rebecca Swan and Beatriz Cash and Ayham Alnabulsi and Murray, {Graeme I.}",
note = "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 = "2017",
month = "6",
day = "6",
doi = "10.1038/bjc.2017.135",
language = "English",
volume = "116",
pages = "1612--1620",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance

AU - Alnabulsi, Abdo

AU - Swan, Rebecca

AU - Cash, Beatriz

AU - Alnabulsi, Ayham

AU - Murray, Graeme I.

N1 - 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 - 2017/6/6

Y1 - 2017/6/6

N2 - Background:Colorectal cancer is a common malignancy and one of the leading causes of cancer-related deaths. The metabolism of omega fatty acids has been implicated in tumour growth and metastasis.Methods:This study has characterised the expression of omega fatty acid metabolising enzymes CYP4A11, CYP4F11, CYP4V2 and CYP4Z1 using monoclonal antibodies we have developed. Immunohistochemistry was performed on a tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosa.Results:The differential expression of CYP4A11 and CYP4F11 showed a strong association with survival in both the whole patient cohort (hazard ratio (HR)=1.203, 95% CI=1.092–1.324, χ2=14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95% CI=1.095–1.488, χ2=9.988, P=0.007). Multivariate analysis revealed that the differential expression of CYP4A11 and CYP4F11 was independently prognostic in both the whole patient cohort (P=0.019) and in mismatch repair proficient tumours (P=0.046).Conclusions:A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours.

AB - Background:Colorectal cancer is a common malignancy and one of the leading causes of cancer-related deaths. The metabolism of omega fatty acids has been implicated in tumour growth and metastasis.Methods:This study has characterised the expression of omega fatty acid metabolising enzymes CYP4A11, CYP4F11, CYP4V2 and CYP4Z1 using monoclonal antibodies we have developed. Immunohistochemistry was performed on a tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosa.Results:The differential expression of CYP4A11 and CYP4F11 showed a strong association with survival in both the whole patient cohort (hazard ratio (HR)=1.203, 95% CI=1.092–1.324, χ2=14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95% CI=1.095–1.488, χ2=9.988, P=0.007). Multivariate analysis revealed that the differential expression of CYP4A11 and CYP4F11 was independently prognostic in both the whole patient cohort (P=0.019) and in mismatch repair proficient tumours (P=0.046).Conclusions:A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours.

KW - biomarker

KW - colorectal cancer

KW - cytochrome P450

KW - omega fatty acid

KW - prognosis

KW - BREAST-CANCER

KW - MICROSATELLITE INSTABILITY

KW - MATRIX METALLOPROTEINASES

KW - HUMAN CYTOCHROME-P450

KW - CELL-PROLIFERATION

KW - PROSTATE-CANCER

KW - COLON-CANCER

KW - METASTASIS

KW - INHIBITORS

KW - GROWTH

U2 - 10.1038/bjc.2017.135

DO - 10.1038/bjc.2017.135

M3 - Article

VL - 116

SP - 1612

EP - 1620

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 12

ER -