This application is in response to RFA-DK-02-017: MPSA Consortium. The major goal of this application is to assemble a cross-disciplinary group of investigators to identify potential biomarkers that can distinguish benign prostatic hyperplasia (BPH) from prostate cancer and normal prostate. The second goal of this application is to validate these potential biomarkers in a larger context, including the use of well-characterized samples from the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial. Specifically, we will: 1. Identify disease specific biomarkers in microdissected prostate tissues by surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry; 2. Identify and characterize isoforms of prostate specific antigen (PSA) and the various members of the human kallikrein family by immunosorption and tandem mass spectrometry (ms/ms)-based sequence identification; 3. Identify secreted proteins in serum of patients with benign prostatic hyperplasia and prostate cancer by SELDI-TOF approaches, and to mine these proteomics data to create predictive models that can stratify samples according to clinical information by using a biomarker patterns recognition software and longitudinal screening algorithms; 4. Identify potential chromosomal locations of under- and over-expressed genes between BPH, prostate cancer, and normal prostate by using a simple rapid overview of expression patterns on metaphase chromosomes; and 5. Collaborate with other investigators in the MPSA Consortium by developing a BWH Prostate Bio-Specimen and Informatics Repository consisting of: 1) the acquisition and maintenance of BWH specimens, both serum and limited tissues; 2) the maintenance and update of a virtual clinical information and outcome database; and 3) the storage of remaining RNA, cDNA, and/or protein extracts from dissected specimens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK063665-03
Application #
6769413
Study Section
Special Emphasis Panel (ZDK1-GRB-3 (O1))
Program Officer
Mullins, Christopher V
Project Start
2002-09-30
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$342,445
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Liu, Brian C-S; Dijohnson, Daniel A; O'Rourke, Dennis J (2012) Antibody profiling with protein antigen microarrays in early stage cancer. Expert Opin Med Diagn 6:187-96
O'Rourke, Dennis J; DiJohnson, Daniel A; Caiazzo Jr, Robert J et al. (2012) Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen. Clin Chim Acta 413:561-7
Caiazzo Jr, Robert J; O'Rourke, Dennis J; Barder, Timothy J et al. (2011) Native antigen fractionation protein microarrays for biomarker discovery. Methods Mol Biol 723:129-48
Arruda, David L; Wilson, William C; Nguyen, Crystal et al. (2009) Microelectrical sensors as emerging platforms for protein biomarker detection in point-of-care diagnostics. Expert Rev Mol Diagn 9:749-55
Tassinari, Oliver W; Aponte, Margarita; Caiazzo Jr, Robert J et al. (2008) Immunoregulomics : a serum autoantibody-based platform for transcription factor profiling. Methods Mol Biol 441:163-73
Ehrlich, Joshua R; Tang, Liangdan; Caiazzo Jr, Robert J et al. (2008) The ""reverse capture"" autoantibody microarray : an innovative approach to profiling the autoantibody response to tissue-derived native antigens. Methods Mol Biol 441:175-92
Tassinari, Oliver W; Caiazzo Jr, Robert J; Ehrlich, Joshua R et al. (2008) Identifying autoantigens as theranostic targets: antigen arrays and immunoproteomics approaches. Curr Opin Mol Ther 10:107-15
Mullins, Chris; Lucia, M Scott; Hayward, Simon W et al. (2008) A comprehensive approach toward novel serum biomarkers for benign prostatic hyperplasia: the MPSA Consortium. J Urol 179:1243-56
Mukhopadhyay, Nishit K; Cinar, Bekir; Mukhopadhyay, Lipi et al. (2007) The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer. Mol Endocrinol 21:2056-70
Caiazzo Jr, Robert J; Tassinari, Oliver W; Ehrlich, Joshua R et al. (2007) Autoantibody microarrays for biomarker discovery. Expert Rev Proteomics 4:261-72

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