Proteomics Approaches to Benign Prostatic Hyperplasia.

描述（由申请人提供）： 本申请是对RFA-DK-02-017：MPSA联盟的回应。本申请的主要目标是组建一个跨学科的研究小组，以确定可以区分良性前列腺增生（BPH）与前列腺癌和正常前列腺的潜在生物标志物。本申请的第二个目标是在更大的背景下验证这些潜在的生物标志物，包括使用来自前列腺症状药物治疗（MTOPS）临床试验的充分表征的样品。 具体而言，我们将： 1.通过表面增强激光在显微切割的前列腺组织中识别疾病特异性生物标志物 解吸/电离飞行时间（SELDI-TOF）质谱; 2.通过免疫吸附和基于串联质谱（ms/ms）的序列鉴定来鉴定和表征前列腺特异性抗原（PSA）的同种型和人激肽释放酶家族的各种成员; 3.利用SELDI-TOF技术对前列腺增生和前列腺癌患者血清中的分泌蛋白进行鉴定，并利用生物标志物模式识别软件和纵向筛选算法对这些蛋白质组学数据进行挖掘，建立预测模型，根据临床信息对样本进行分层; 4.通过使用中期染色体上表达模式的简单快速概述，确定BPH，前列腺癌和正常前列腺之间低表达和过表达基因的潜在染色体位置; 5.通过开发BWH前列腺生物标本和信息学储存库与MPSA联盟的其他研究者合作，该储存库包括：1）BWH标本（包括血清和有限组织）的获取和维护; 2）虚拟临床信息和结果数据库的维护和更新;以及3）解剖标本剩余RNA、cDNA和/或蛋白质提取物的存储。

DESCRIPTION (provided by applicant): 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.