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Int J Cancer. 2016 Jul 15;139(2):256-68. doi: 10.1002/ijc.30016. Epub 2016 Feb 23.

Biomarkers in bladder cancer: A metabolomic approach using in vitro and ex vivo model systems.

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UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Cancer Biology & Epigenetics Group, Portuguese Oncology Institute-Porto, Porto, Portugal.
Department of Pathology and Molecular Immunology-Biomedical Sciences Institute Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Department of Pathology, Portuguese Oncology Institute-Porto, Porto, Portugal.
UCIBIO/REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
FP-ENAS, CEBIMED, Fundação Ensino e Cultura Fernando Pessoa, Universidade Fernando Pessoa, Porto, Portugal.


Metabolomics has recently proved to be useful in the area of biomarker discovery for cancers in which early diagnostic and prognostic biomarkers are urgently needed, as is the case of bladder cancer (BC). This article presents a comprehensive review of the literature on the metabolomic studies on BC, highlighting metabolic pathways perturbed in this disease and the altered metabolites as potential biomarkers for BC detection. Current disease model systems used in the study of BC metabolome include in vitro-cultured cancer cells, ex vivo neoplastic bladder tissues and biological fluids, mainly urine but also blood serum/plasma, from BC patients. The major advantages and drawbacks of each model system are discussed. Based on available data, it seems that BC metabolic signature is mainly characterized by alterations in metabolites related to energy metabolic pathways, particularly glycolysis, amino acid and fatty acid metabolism, known to be crucial for cell proliferation, as well as glutathione metabolism, known to be determinant in maintaining cellular redox balance. In addition, purine and pyrimidine metabolism as well as carnitine species were found to be altered in BC. Finally, it is emphasized that, despite the progress made in respect to novel biomarkers for BC diagnosis, there are still some challenges and limitations that should be addressed in future metabolomic studies to ensure their translatability to clinical practice.


biofluids; biomarkers; bladder cancer; cell lines; metabolic pathways; metabolomics; review; serum; tissue; urine

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