2325 AUTOANTIBODY SIGNATURES AS BIOMARKERS TO DISTINGUISH PROSTATE CANCER FROM BENIGN PROSTATIC HYPERPLASIA USING A NATIVE ANTIGEN CAPTURE MICROARRAY PLATFORM

Abstract

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112325 AUTOANTIBODY SIGNATURES AS BIOMARKERS TO DISTINGUISH PROSTATE CANCER FROM BENIGN PROSTATIC HYPERPLASIA USING A NATIVE ANTIGEN CAPTURE MICROARRAY PLATFORM Dennis O'Rourke, Daniel DiJohnson, Michael O'Leary, Jerome Richie, and Brian Liu Dennis O'RourkeDennis O'Rourke Boston, MA More articles by this author , Daniel DiJohnsonDaniel DiJohnson Boston, MA More articles by this author , Michael O'LearyMichael O'Leary Boston, MA More articles by this author , Jerome RichieJerome Richie Boston, MA More articles by this author , and Brian LiuBrian Liu Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2572AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Serum prostate specific antigen (PSA) levels lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We now report the identification of 5 autoantibody signatures to specific cancer targets which may be capable of ruling out a diagnosis of cancer for patients with non-malignant prostatic disease, such as BPH, in patients with elevated serum PSA. METHODS To discover new biomarkers which may distinguish between prostate cancer and BPH, a native antigen capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nano-particle slides to capture native antigens from prostate cancer cells. Using the immobilized antigens as baits, autoantibodies from prostate cancer patients and patients with BPH can be isolated and probed. From preliminary experiments using an initial set of over 500 cancer related antigens, a customized array containing 27 unique antigens was further tested. Prostate cancer patient (n=41) and BPH patient serum samples with a mean follow-up of 6.8 years without the diagnosis of cancer (n=39) were obtained. 100ug of IgGs were purified and dye labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. For each spot, a signal-to-noise ratio (SNR) was measured to eliminate background interference. Through comparative analysis of the prostate cancer arrays and the BPH arrays, autoantibody signatures were identified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined for the 27 antigens. RESULTS Using the native antigen capture microarray platform, we found unique autoantibody signatures capable of distinguishing between prostate cancer and BPH. A SNR was calculated for each autoantibody reactivity on each array and compared. The top 5 autoantibody signatures were found to react with TARDBP, TLN1, PARK7, PSIP1, and CALD1. Combining these antigens resulted in an AUC of 0.95 compared to 0.50 for PSA when differentiating between prostate cancer and BPH in our cohort. In addition, the coefficient of variance between duplicate runs for a given sample averaged 14.8% (range 11%–22%). CONCLUSIONS Our results demonstrate the ability of a native antigen capture microarray platform to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with elevated PSA. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e932 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dennis O'Rourke Boston, MA More articles by this author Daniel DiJohnson Boston, MA More articles by this author Michael O'Leary Boston, MA More articles by this author Jerome Richie Boston, MA More articles by this author Brian Liu Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...