title: Can urinary exosomes act as treatment response markers in prostate cancer?
abstract: BACKGROUND
  Recently, nanometer sized vesicles (termed exosomes) have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy.
  
  
  METHODS
  Ten patients (with locally advanced PCa) provided spot urine specimens at three time points during standard therapy. Patients received 3-6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA) and tumour-associated marker 5T4 was examined.
  
  
  RESULTS
  The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8) patient.
  
  
  CONCLUSIONS
  Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide clinically useful information.
authors.affiliation: Section of Oncology & Palliative Medicine, School of Medicine, Cardiff University, Velindre Cancer Centre, Whitchurch, Cardiff, UK. Paul.Mitchell@velindre-tr.wales.nhs.uk
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mitchell
authors.forename: Joanne
authors.initials: J
authors.lastname: Welton
authors.forename: John
authors.initials: J
authors.lastname: Staffurth
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Court
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Tabi
authors.forename: Aled
authors.initials: A
authors.lastname: Clayton
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000652:urine; D045744:Cell Line, Tumor; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy / Q000652:urine*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor