Metabolomic credentialing of murine carcinogen-induced urothelial cancer

Sci Rep. 2021 Nov 11;11(1):22085. doi: 10.1038/s41598-021-99746-3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Butylhydroxybutylnitrosamine / toxicity*
  • Carcinogens / toxicity*
  • Cell Line
  • Humans
  • Male
  • Metabolome* / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urothelium / drug effects*
  • Urothelium / metabolism
  • Urothelium / pathology

Substances

  • Carcinogens
  • Butylhydroxybutylnitrosamine