title: Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.
abstract: The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans.
  
  
  
  The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2.
  
  
  
  In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560-0.788), ERG (AUC 0.785 (CI:0.680-0.890), PCA3 (AUC 0.681 (CI:0.567-0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600-0.888), and TMPRSS2 (AUC 0.637 (CI:0.519-0.754).
  
  
  
  This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Piruz
authors.initials: P
authors.lastname: Motamedinia
authors.affiliation: Exosome Diagnostics, Inc. New York, New York, United States of America.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Scott
authors.affiliation: Exosome Diagnostics, Inc. New York, New York, United States of America.
authors.forename: Kendall L
authors.initials: KL
authors.lastname: Bate
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Neda
authors.initials: N
authors.lastname: Sadeghi
authors.affiliation: Exosome Diagnostics, Inc. New York, New York, United States of America.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Salazar
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Edan
authors.initials: E
authors.lastname: Shapiro
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Lipsky
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Greg W
authors.initials: GW
authors.lastname: Hruby
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Ketan K
authors.initials: KK
authors.lastname: Badani
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
authors.affiliation: Exosome Diagnostics, Inc. New York, New York, United States of America.|Department of Pathology, Icahn School of Medicine at Mt. Sinai, New York, New York, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Donovan
authors.affiliation: Exosome Diagnostics, Inc. New York, New York, United States of America.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Comper
authors.affiliation: Department of Urology, Columbia University Medical Center, Department of Urology, New York, New York, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
authors.affiliation: Exosome Diagnostics, Inc. New York, New York, United States of America.
authors.forename: Leileata M
authors.initials: LM
authors.lastname: Russo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine; D016022:Case-Control Studies; D055354:Exosomes / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010865:Pilot Projects; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000652:urine*; D012334:RNA, Neoplasm / Q000235:genetics* / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; C515553:TMPRSS2-ERG fusion protein, human