A Comprehensive Approach Toward Novel Serum Biomarkers for Benign Prostatic Hyperplasia: The MPSA Consortium

Abstract

Purpose-Clinical benign prostatic hyperplasia (BPH) is primarily diagnosed based on a diverse array of progressive lower urinary tract symptoms (LUTS) and is likely distinct from histological BPH, which is detected by the presence of non-malignant proliferation of prostate cells but may or may not be associated with symptoms. Pharmacological management of LUTS has emerged as an effective initial treatment for clinical BPH due to the introduction of new drug therapies shown to be effective in recent large clinical trials. Despite advances in symptom management and research into BPH pathology, diagnostic strategies for prediction of BPH progression and response to drug modalities are lacking and questions remain as to the molecular differences underlying clinical (symptomatic) versus histological (non-symptomatic) BPH. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-To date the MPSA has identified a number of promising biomarkers and other molecular and cellular changes associated with BPH. NIH Public AccessConclusions-These findings and ongoing consortium discovery efforts have the potential to provide a greater understanding of the defects underlying disease pathology and may lead to the development of early and more effective pharmacological treatment strategies for BPH.

Personalized Medicine for the Management of Benign Prostatic Hyperplasia

“…Recognizing the importance of targeted therapies for management of BPH, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the MTOPS Prostatic Samples Analysis (MPSA) Consortium in 2002 to “identify and validate molecular markers that may better define BPH-related pathologies, identify risk of progression of LUTS, and predict response to drug therapy.” 31 Since its establishment, the group has developed a variety of methodologies for acquiring and processing tissue, extracting genetic information, and analyzing potential biomarkers and therapeutic targets. The aforementioned gene expression analysis comparing clinical BPH to histologic BPH identified a novel biomarker JM-27.…”

“…Next, a serum-based ELISA assay was developed using an anti-JM-27 monoclonal antibody which could measure serum levels of JM-27 and distinguish between symptomatic and asymptomatic BPH patient sets. 31, 32 Unlike PSA, serum JM-27 levels are not affected by prostate volume, giving JM-27 potential as a biomarker that could be obtained as a diagnostic blood test to risk stratify patients for symptom and disease progression However, additional studies are needed to validate these initial results amongst a larger sample size in order to demonstrate the utility of JM-27.…”

A Novel Multidimensional Protein Identification Technology Approach Combining Protein Size Exclusion Prefractionation, Peptide Zwitterion−Ion Hydrophilic Interaction Chromatography, and Nano-Ultraperformance RP Chromatography/nESI-MS2 for the in-Depth Analysis of the Serum Proteome and Phosphoproteome: Application to Clinical Sera Derived from Humans with Benign Prostate Hyperplasia

“…As part of the hallmark Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial, the Prostatic Samples Analysis (MPSA) Consortium attempted to establish and validate potential biomarkers that could stratify the BPH patients according to their response to medical therapy, by using dual antibody sandwich immunoassay of ELISA, which is the most sensitive bioassay technique currently available. 43,44 However, this was an a priori approach targeting specific biomarkers that bypassed the possibility of observing a plethora of low-abundance proteins that might play a significant role on the differential diagnosis between BPH and PCa. Along this theme, the proposed MudPIT approach A, used as a qualitative protein identification tool in this study, can be extended to include relative quantitative features made possible with the use of multiplex stable isotope labeling strategies at the protein or peptide level to further minimize analytical systematic error and to better stratify patients in accordance with prostate pathophysiology analogous to that of the BPH/PCa prostate tissue study reported by the authors.…”

The Discovery of Cancer Tissue Specific Proteins in Serum: Case Studies on Prostate Cancer

“…In contrast, the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial, attempted to characterize potential biomarkers that could stratify the BPH patients according to their response to medical therapy, by using the a priori use of the ELISA assay (Mullins et al, 2008). However, such an a priori approach bypassed the possibility in observing unexpected low-abundant tissue specific and secreted proteins that might play a significant role on the differential diagnosis between BPH and PCa.…”