Metabolomic credentialing of murine carcinogen-induced urothelial cancer

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 thera...

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Bibliographic Details
Published in:Scientific reports 2021-11, Vol.11 (1), p.22085-13, Article 22085
Main Authors: Afify, Hesham, Ghoneum, Alia, Almousa, Sameh, Abdulfattah, Ammar Yasser, Warren, Bailey, Langsten, Kendall, Gonzalez, Daniela, Casals, Randy, Bharadwaj, Manish, Kridel, Steven, Said, Neveen
Format: Article
Language:English
Subjects:
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Animal models
Animals
Bladder cancer
Butylhydroxybutylnitrosamine - toxicity
Carcinogenesis
Carcinogens
Carcinogens - toxicity
Cell Line
Heterogeneity
Humanities and Social Sciences
Humans
Invasiveness
Lipid metabolism
Male
Malignancy
Metabolism
Metabolome - drug effects
Metabolomics
Mice
Mice, Inbred C57BL
multidisciplinary
Neoplasms, Experimental - chemically induced
Neoplasms, Experimental - metabolism
Neoplasms, Experimental - pathology
Science
Science (multidisciplinary)
Urinary Bladder Neoplasms - chemically induced
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
Urothelial cancer
Urothelium - drug effects
Urothelium - metabolism
Urothelium - pathology
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-99746-3