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.
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 language | English |
|---|---|
| Pages (from-to) | 1612-1620 |
| Number of pages | 9 |
| Journal | British Journal of Cancer |
| Volume | 116 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 6 Jun 2017 |
Bibliographical 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.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
