Benign prostatic hyperplasia (BPH) is an extremely common disease of men over age 50. Seventy percent of men by age 60 and 90% by age 70 have histologic evidence of BPH. BPH is clinically manifested by a cluster of lower urinary tract symptoms. A significant cohort of these older individuals exhibit clinical symptoms of BPH. The precise molecular mediators of BPH have yet to be discovered, however, there is considerable evidence that androgens and race play an important role in this process. Before prognostic markers and rational therapies can be developed to target clinically symptomatic BPH, the molecular alterations associated with it need to be unmasked. Our overall hypothesis is that a distinct set of genes/proteins define BPH, molecularly distinguishing it from prostate cancer and non-hyperplastic benign prostatic epithelia. These """"""""signature"""""""" molecules have potential as prognostic markers, therapeutic targets, and may play a role in BPH development or progression. The advent of high throughput genomic and proteomic techniques raises new hopes for identifying novel molecular targets for therapy. In this proposal, we will take a functional genomics approach to molecularly dissect BPH.
In Aims 1 and 2, gene and protein expression profiles of BPH will be determined using high-density cDNA microarrays and protein microarrays, respectively.
Aims 3 and 4 will validate candidate tissue and serum markers using both local and MTOPS samples. Given this, the specific aims are as follows:
Aim 1 : Define gene expression profiles of BPH.
Aim 2 : Define focused proteomic profiles of prostatic tissue from BPH patients.
Aim 3 : Validation of candidate tissue biomarkers of symptomatic BPH a) Tissue Microarray (TMA) Validation using Michigan samples. b) Validation of tissue markers using MTOPS samples.
Aim 4 : Validation of candidate serum biomarkers of symptomatic BPH. a) Serum Microarray Validation using Michigan samples. b) Validation of serum markers using MTOPS samples.
| 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 |
| Dhanasekaran, Saravana Mohan; Dash, Atreya; Yu, Jianjun et al. (2005) Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty. FASEB J 19:243-5 |
