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

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, χ=14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95% CI=1.095-1.488, χ=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.