Urinary lipid production in dogs with urothelial carcinoma

Canine urothelial carcinoma (cUC) is a prevalent and aggressive malignancy in dogs. Current treatments have limited effectiveness, and delays in diagnosis are often a concern. cUC is unique in that it shows high responsiveness to cyclooxygenase (COX) inhibitors and has a high frequency of a single nucleotide mutation in BRAF, known as BRAF^V595E. COX is one of the key enzymes involved in the production of lipid mediators, which regulate the progression of various diseases. Although studies have revealed the roles of COX in cUC, the production profiles of lipid mediators remain unknown. In this study, we comprehensively measured the urinary lipid mediator levels of cUC dogs using liquid chromatography-tandem mass spectrometry. We found that lipid production was altered in cUC, with increased amounts of several COX-catalyzed lipids, including prostaglandin E₂ and thromboxane B₂, and several lipoxygenase-catalyzed lipids, including leukotriene E₄. Additionally, we found that the BRAF^V595E mutation tended to increase the levels of most enzymatically produced lipids. Our results provide insights into novel therapeutic and diagnostic strategies for cUC and cancers with BRAF mutations.