title: Identification of prostate cancer biomarkers in urinary exosomes.
abstract: Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.
authors.affiliation: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Øverbye
authors.affiliation: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tore
authors.initials: T
authors.lastname: Skotland
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Koehler
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Bernd
authors.initials: B
authors.lastname: Thiede
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
authors.affiliation: Department of Urology, Oslo University Hospital, 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, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Biosciences, University of Oslo, 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, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
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*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000652:urine*; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000652:urine*; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D053719:Tandem Mass Spectrometry; D016482:Urinalysis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: biomarkers; exosomes; extracellular vesicles; mass spectrometry; prostate cancer