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...

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Main Authors: Hesham Afify, Alia Ghoneum, Sameh Almousa, Ammar Yasser Abdulfattah, Bailey Warren, Kendall Langsten, Daniela Gonzalez, Randy Casals, Manish Bharadwaj, Steven Kridel, Neveen Said
Format: Article
Language:English
Published: Nature Portfolio 2021-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-99746-3
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author Hesham Afify
Alia Ghoneum
Sameh Almousa
Ammar Yasser Abdulfattah
Bailey Warren
Kendall Langsten
Daniela Gonzalez
Randy Casals
Manish Bharadwaj
Steven Kridel
Neveen Said
author_facet Hesham Afify
Alia Ghoneum
Sameh Almousa
Ammar Yasser Abdulfattah
Bailey Warren
Kendall Langsten
Daniela Gonzalez
Randy Casals
Manish Bharadwaj
Steven Kridel
Neveen Said
author_sort Hesham Afify
collection DOAJ
description 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.
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spelling doaj.art-9642edddfaa74bfa8f06a1f1d2f9bd3a2022-12-22T04:03:53ZengNature PortfolioScientific Reports2045-23222021-11-0111111310.1038/s41598-021-99746-3Metabolomic credentialing of murine carcinogen-induced urothelial cancerHesham Afify0Alia Ghoneum1Sameh Almousa2Ammar Yasser Abdulfattah3Bailey Warren4Kendall Langsten5Daniela Gonzalez6Randy Casals7Manish Bharadwaj8Steven Kridel9Neveen Said10Department of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineCell Analysis Division, Agilent Technologies, IncDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineDepartment of Cancer Biology, Medical Center Boulevard, Wake Forest University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-021-99746-3
spellingShingle Hesham Afify
Alia Ghoneum
Sameh Almousa
Ammar Yasser Abdulfattah
Bailey Warren
Kendall Langsten
Daniela Gonzalez
Randy Casals
Manish Bharadwaj
Steven Kridel
Neveen Said
Metabolomic credentialing of murine carcinogen-induced urothelial cancer
Scientific Reports
title Metabolomic credentialing of murine carcinogen-induced urothelial cancer
title_full Metabolomic credentialing of murine carcinogen-induced urothelial cancer
title_fullStr Metabolomic credentialing of murine carcinogen-induced urothelial cancer
title_full_unstemmed Metabolomic credentialing of murine carcinogen-induced urothelial cancer
title_short Metabolomic credentialing of murine carcinogen-induced urothelial cancer
title_sort metabolomic credentialing of murine carcinogen induced urothelial cancer
url https://doi.org/10.1038/s41598-021-99746-3
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