Oxylipin patterns in human colon adenomas

Objective: Cyclooxygenase (COX)-derived prostaglandin E-2 (PGE(2)) is an important lipid mediator in colorectal carcinoma (CRC) pathogenesis. Other lipid mediators derived from lipoxygenases (LOX) have also been implicated in neoplastic processes in the colon. In this study we aimed to characterize lipid mediators, so called oxylipins, in human colon adenomatous polyps. Design: We quantified oxylipins in healthy colon tissue and colorectal adenoma tissue procured during routine colonoscopy examinations. Lipid metabolite profiles were analyzed by liquid chromatography-tandem mass spectrometry. Results: Adenoma tissue showed a distinct prostaglandin profile as compared to normal colon mucosa. Interestingly, PGE(2) was not higher in adenoma tissue as compared to normal mucosa. In contrast, we found significantly lower levels of prostaglandin D-2, prostaglandin J(2), and prostaglandin D-1 in adenoma tissue. Furthermore, levels of 5-LOX and 12-LOX pathway products were clearly increased in adenoma biopsy samples. We also investigated the effect of aspirin treatment on prostaglandin profiles in adenoma tissue in a subset of patients and found a trend towards decreased prostaglandin levels in response to aspirin. Conclusion: The human data presented here show specific changes of oxylipin profiles in colon adenoma tissue with decreased prostaglandin D-2 levels as well as increased 5-and 12-LOX metabolites.