Proteomics Approaches to Benign Prostatic Hyperplasia.

描述(由申请人提供)： 本申请是对RFA-DK-02-017：MPSA联合体的响应。这项应用的主要目标是召集一个跨学科的研究小组，以确定可以区分良性前列腺增生症(BPH)与前列腺癌和正常前列腺的潜在生物标志物。这项应用的第二个目标是在更大的背景下验证这些潜在的生物标记物，包括使用来自前列腺症状医学治疗(MTOPS)临床试验的具有良好特征的样本。 具体来说，我们会： 1.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)质谱仪； 2.通过免疫吸附和串联质谱仪(MS/MS)序列鉴定鉴定前列腺特异性抗原(PSA)的异构体和人激肽释放酶家族的不同成员； 3.用SELDI-TOF方法鉴定良性前列腺增生症和前列腺癌患者血清中的分泌性蛋白质，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数据进行挖掘，建立能够根据临床信息对样本进行分层的预测模型； 4.通过对中期染色体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表达不足和过度表达的基因的潜在染色体位置；以及 5.与MPSA联盟中的其他研究人员合作，开发BWH前列腺生物标本和信息库，包括：1)获取和维护BWH血清和有限组织的标本；2)维护和更新虚拟临床信息和结果数据库；以及3)存储来自解剖标本的剩余RNA、cDNA和/或蛋白质提取物。

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.