title: Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer.
abstract: BACKGROUND
  The objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients.
  
  
  METHODS
  Quantitative iTRAQ LC/LC/MS/MS analysis was used to identify proteins that are differentially expressed in the urine of men with BPH compared with those who have localized PCa. These proteins were validated in 173 urine samples from patients diagnosed with BPH (N = 83) and PCa (N = 90). Multivariate logistic regression analysis was used to identify the predictive biomarkers.
  
  
  RESULTS
  Three proteins, β2M, PGA3, and MUC3 were identified by iTRAQ and validated by immunoblot analyses. Univariate analysis demonstrated significant elevations in urinary β2M (P < 0.001), PGA3 (P = 0.006), and MUC3 (P = 0.018) levels found in the urine of PCa patients. Multivariate logistic regression analysis revealed AUC values ranging from 0.618 for MUC3 (P = 0.009), 0.625 for PGA3 (P < 0.008), and 0.668 for β2M (P < 0.001). The combination of all three demonstrated an AUC of 0.710 (95% CI: 0.631 - 0.788, P < 0.001); diagnostic accuracy improved even more when these data were combined with PSA categories (AUC = 0.812, (95% CI: 0.740 - 0.885, P < 0.001).
  
  
  CONCLUSIONS
  Urinary β2M, PGA3, and MUC3, when analyzed alone or when multiplexed with clinically defined categories of PSA, may be clinically useful in noninvasively resolving the dilemma of effectively discriminating between BPH and localized PCa.
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. andrej.jedinak@childrens.harvard.edu.|Harvard Medical School, Boston, MA, USA. andrej.jedinak@childrens.harvard.edu.
authors.forename: Andrej
authors.initials: A
authors.lastname: Jedinak
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. adamcuratolo@gmail.com.
authors.forename: Adam
authors.initials: A
authors.lastname: Curatolo
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. david.zurakowski@childrens.harvard.edu.|Department of Anesthesia, Boston Children's Hospital, Boston, MA, USA. david.zurakowski@childrens.harvard.edu.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: Harvard Medical School, Boston, MA, USA. sdillion1@bidmc.harvard.edu.|Genomics and Proteomics Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. sdillion1@bidmc.harvard.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: Dillon
authors.affiliation: Harvard Medical School, Boston, MA, USA. bhasin@bidmc.harvard.edu.|Genomics and Proteomics Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. bhasin@bidmc.harvard.edu.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Bhasin
authors.affiliation: Harvard Medical School, Boston, MA, USA. tliberma@bidmc.harvard.edu.|Genomics and Proteomics Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. tliberma@bidmc.harvard.edu.
authors.forename: Towia A
authors.initials: TA
authors.lastname: Libermann
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. roopali.roy@childrens.harvard.edu.|Harvard Medical School, Boston, MA, USA. roopali.roy@childrens.harvard.edu.
authors.forename: Roopali
authors.initials: R
authors.lastname: Roy
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. sachdev.monisha@gmail.com.
authors.forename: Monisha
authors.initials: M
authors.lastname: Sachdev
authors.affiliation: Harvard Medical School, Boston, MA, USA. kloughlin@partners.org.|Department of Urology, Brigham and Women's Hospital, Boston, MA, USA. kloughlin@partners.org.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Loughlin
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. marsha.moses@childrens.harvard.edu.|Harvard Medical School, Boston, MA, USA. marsha.moses@childrens.harvard.edu.
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000652:urine; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000652:urine; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000652:urine*; D020543:Proteome / Q000378:metabolism; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome