Metabolomic credentialing of murine carcinogen-induced urothelial cancer

Abstract

Bladder cancer (BCa) is the most common malignancy of the urinary system with increasing incidence, mortality, and limited treatment options. Therefore, it is imperative to validate preclinical models that faithfully represent BCa cellular, molecular, and metabolic heterogeneity to develop new therapeutics. We performed metabolomic profiling of premalignant and non-muscle invasive bladder cancer (NMIBC) that ensued in the chemical carcinogenesis N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model. We identified the enriched metabolic signatures that associate with premalignant and NMIBC. We found that enrichment of lipid metabolism is the forerunner of carcinogen-induced premalignant and NMIBC lesions. Cross-species analysis revealed the prognostic value of the enzymes associated with carcinogen-induced enriched metabolic in human disease. To date, this is the first study describing the global metabolomic profiles associated with early premalignant and NMIBC and provide evidence that these metabolomic signatures can be used for prognostication of human disease.

Non-Invasive Imaging Modalities in Intravesical Murine Models of Bladder Cancer

“…Current intravesical murine models of BCa include carcinogen-induced, orthotopic, transgenic, or humanized mice [ 12 , 13 , 14 , 15 ]. Carcinogenic models are developed by the oral administration of chemical carcinogens, which have been reported to recapitulate the progression of human BCa [ 16 , 17 , 18 ]. However, tumors make take as long as several months to develop using this method [ 19 , 20 ].…”