LC-MS Metabolomics of Urine Reveals Distinct Profiles for Low- and High-Grade Bladder Cancer
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ABSTRACT: Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures such as cystoscopy. Our aim was to discover novel urine metabolomic profiles to diagnose and stage non-muscle invasive (NMIBC) and muscle-invasive (MIBC) patients using ultra-performance liquid chromatography analysis (UPLC)-based metabolomics. We prospectively recruited 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). We conducted a UPLC-quadrupole-time-of-flight mass spectrometry (UPLC-Q-ToF MS) untargeted metabolomic analysis in all urine samples. We selected the discriminant variables between groups with a supervised orthogonal-least-squares discriminant analysis (OPLS-DA) analysis and we identified them by querying their exact mass against those presented in online databases through a mediator platform. Subsequently, we confirmed the dysregulated metabolites when chemical standards were commercially available. We compared all clinical groups of patients with controls and we identified dysregulated metabolites in every comparison. Of these, we confirmed p-cresol glucuronide as potential diagnostic biomarker, and potential staging tool for NMIBC patients. Among NMIBC patients, we identified p-coumaric acid as a potential staging biomarker for milder NMIBC stages (TaG1). Additionally, we confirmed spermine and adenosine as potential staging biomarkers for MIBC. This is the first study conducted in urine samples of most stages of NMIBC and MIBC and healthy controls to identify non-invasive biomarkers. Once confirmed, these may improve BC management thus reducing the use of current harmful diagnostic techniques.
ORGANISM(S): Human Homo Sapiens
TISSUE(S): Urine
DISEASE(S): Cancer
SUBMITTER: Marta Roca Marugán
PROVIDER: ST001662 | MetabolomicsWorkbench | Thu Jan 21 00:00:00 GMT 2021
REPOSITORIES: MetabolomicsWorkbench
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