Mouse anti-Human CYP4F11 monoclonal antibody, clone G32 Q7 G6

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, chi(2) = 14.968, P = 0.001) and in mismatch repair-proficient tumours (HR = 1.276, 95% CI = 1.095-1.488, chi(2) = 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.

The efficacy of erlotinib treatment for advanced non-small cell lung cancer (NSCLC) is due to its action as an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Patients treated with erlotinib experience different drug responses. The effect of germline mutations on therapeutic responses and adverse drug responses (ADRs) to erlotinib in Chinese patients requires elucidation. Sixty Han Chinese advanced non-small cell lung cancer patients received erlotinib monotherapy and, for each participant, 76 candidate genes (related to EGFR signaling, drug metabolism and drug transport pathways) were sequenced and analyzed. The single-nucleotide polymorphisms (SNPs) rs1042640 in UGT1A1 0, rs1060463, and rs1064796 in CYP4F11, and rs2074900 in CYP4F2 were significantly associated with therapeutic responses to erlotinib. Psi 064796 in CYP4F11 and rs10045685 in UGT3A1 were significantly associated with adverse drug reaction. Moreover, analysis of a validation cohort confirmed the significant association between rs10045685 in UGT3A1 and erlotinib adverse drug response(unadjusted p = 0.015). This study provides comprehensive, systematic analyses of genetic variants associated with responses to erlotinib in Chinese advanced non-small cell lung cancer patients. Newly-identified SNPs may serve as promising markers to predict responses and safety in erlotinib-treated advanced non-small cell lung cancer patients after chemotherapy doublet.