Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression.
Marc Clos-GarciaAna Loizaga-IriartePatricia Zuñiga-GarciaPilar Sánchez-MosqueraAna Rosa CortazarEsperanza GonzálezVerónica TorranoCristina AlonsoMiriam Pérez-CormenzanaAitziber Ugalde-OlanoIsabel Lacasa-ViscasillasAzucena CastroFelix RoyoMiguel UndaArkaitz CarracedoJuan M Falcón-PérezPublished in: Journal of extracellular vesicles (2018)
Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography-mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundance between PCa and BPH. Interestingly, urine EVs recapitulated many of the metabolic alterations reported in PCa, including phosphathidylcholines, acyl carnitines, citrate and kynurenine. Importantly, we found elevated levels of the steroid hormone, 3beta-hydroxyandros-5-en-17-one-3-sulphate (dehydroepiandrosterone sulphate) in PCa urinary EVs, in line with the potential elevation of androgen synthesis in this type of cancer. This work supports urinary EVs as a non-invasive source to infer metabolic changes in PCa.
Keyphrases
- prostate cancer
- ms ms
- mass spectrometry
- benign prostatic hyperplasia
- radical prostatectomy
- end stage renal disease
- lower urinary tract symptoms
- newly diagnosed
- ejection fraction
- ultra high performance liquid chromatography
- antibiotic resistance genes
- tandem mass spectrometry
- peritoneal dialysis
- amino acid
- small molecule
- squamous cell carcinoma
- prognostic factors
- high throughput
- drug delivery
- papillary thyroid
- cancer therapy
- high performance liquid chromatography
- simultaneous determination
- high resolution mass spectrometry
- young adults
- patient reported outcomes