title: Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.
abstract: BACKGROUND
  Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA.
  
  
  METHODS
  To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined.
  
  
  RESULTS
  Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity).
  
  
  CONCLUSIONS
  Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA.
authors.affiliation: Molecular Urology Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: O'Rourke
authors.forename: Daniel A
authors.initials: DA
authors.lastname: DiJohnson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Caiazzo
authors.forename: James C
authors.initials: JC
authors.lastname: Nelson
authors.forename: David
authors.initials: D
authors.lastname: Ure
authors.forename: Michael P
authors.initials: MP
authors.lastname: O'Leary
authors.forename: Jerome P
authors.initials: JP
authors.lastname: Richie
authors.forename: Brian C-S
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011470:Prostatic Hyperplasia / Q000097:blood* / Q000175:diagnosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis; D040081:Protein Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D017430:Prostate-Specific Antigen