title: Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach.
abstract: The incidence and rate of recurrence of bladder cancer is high, particularly in developed countries, however current methods for diagnosis are limited to detecting high-grade tumours using often invasive methods. A panel of biomarkers to characterise tumours of different grades that could also distinguish between patients exhibiting the disease with first incidence or recurrence could be useful for bladder cancer diagnostics. In this study, potential metabolic biomarkers have been discovered through mass spectrometry based metabolomics of urine. Pre-treatment urine samples were collected from 48 patients diagnosed of urothelial bladder cancer. Patients were followed-up through the hospital pathological charts to identify whether and when the disease recurred or progressed. Subsequently, they were classified according to whether or not they suffered a tumour recurrence (recurrent or stable) as well as their risk group according to tumour grade and stage. Identified metabolites have been analysed in terms of disease characteristics (tumour stage and recurrence) and have provided an insight into bladder cancer progression. Using both liquid chromatography and capillary electrophoresis-mass spectrometry, a total of 27 metabolite features were highlighted as significantly different between patient groups. Some, for example histidine, phenylalanine, tyrosine and tryptophan have been previously linked with bladder cancer, however until now their connection with bladder cancer progression has not been previously reported. The candidate biomarkers revealed in this study could be useful in the clinic for diagnosis of bladder cancer and, through characterising the stage of the disease, could also be useful in prognostics.
authors.affiliation: CEMBIO, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain; IQSC, Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, São Paulo, Brazil.
authors.forename: Juliana Vieira
authors.initials: JV
authors.lastname: Alberice
authors.forename: Andre F S
authors.initials: AF
authors.lastname: Amaral
authors.forename: Emily Grace
authors.initials: EG
authors.lastname: Armitage
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Lorente
authors.forename: Ferrán
authors.initials: F
authors.lastname: Algaba
authors.forename: Emanuel
authors.initials: E
authors.lastname: Carrilho
authors.forename: Mirari
authors.initials: M
authors.lastname: Márquez
authors.forename: Antonia
authors.initials: A
authors.lastname: García
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D018450:Disease Progression; D019075:Electrophoresis, Capillary / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D012008:Recurrence; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000652:urine*
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Bladder cancer; Metabolomics; Progression; Urine