title: Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers.
abstract: Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers.
  
  
  
  A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls.
  
  
  
  Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed.
  
  
  
  This study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers.
authors.affiliation: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.
authors.forename: Tore
authors.initials: T
authors.lastname: Skotland
authors.affiliation: Zora Biosciences Oy, 02150 Espoo, Finland.
authors.forename: Kim
authors.initials: K
authors.lastname: Ekroos
authors.affiliation: Zora Biosciences Oy, 02150 Espoo, Finland.
authors.forename: Dimple
authors.initials: D
authors.lastname: Kauhanen
authors.affiliation: Zora Biosciences Oy, 02150 Espoo, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Simolin
authors.affiliation: Division of Radiology and Nuclear Medicine, Oslo University Hospital, 0379 Oslo, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
authors.affiliation: Department of Urology, Oslo University Hospital, 0586 Oslo, Norway.
authors.forename: Viktor
authors.initials: V
authors.lastname: Berge
authors.affiliation: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway; Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
authors.affiliation: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway. Electronic address: Alicia.Martinez.Llorente@rr-research.no.
authors.forename: Alicia
authors.initials: A
authors.lastname: Llorente
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D055354:Exosomes / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D011467:Prostate / Q000737:chemistry / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D008055:Lipids
keywords: Diagnostics; Exosomes; Extracellular vesicles; High-throughput quantitative lipidomics; Lipids; Liquid biopsy; Non-invasive biomarkers; Prostate cancer; Urine