CIC bioGUNE
Published May 7, 2018 | Version v1
Journal article Open

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Authors/Creators

  • 1. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain;
  • 2. Department of Urology, Basurto University Hospital, Bilbao, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC);
  • 3. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC);
  • 4. OWL Metabolomics, Bizkaia Technology Park, Derio, Spain
  • 5. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Department of Pathology, Basurto University Hospital, Bilbao, Spain
  • 6. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD);
  • 7. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Ikerbasque, Basque foundation for science, Bilbao, Spain; Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bilbao, Spain
  • 8. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD); Ikerbasque, Basque foundation for science, Bilbao, Spain;

Description

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 ultrahigh-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 hosphathidylcholines, 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.

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