MTOPS Prostate Samples Analysis Consortium

描述（由申请人提供）： UT西南前列腺疾病中心的研究人员已经合作了十多年，从基础，转化和临床研究前景研究良性前列腺增生（BPH）的发病机制。我们的研究者为NIDDKK资助的MTOPS试验的设计、监督和实施提供了主要领导。此外，该小组已经开发了大量的初步数据，证明了几种生物标志物在BPH进展中的作用。基于这一初步证据，我们建议专门验证以下生物标志物（或生物标志物家族）作为BPH进展的标志物：前列腺平滑肌收缩蛋白表型、前列腺α-2巨球蛋白和2型5a-还原酶。将使用UT Southwestern NIDDK资助的乔治W.奥布莱恩组织库，其中包含600多个BPH样本和适当的控制。在检测验证后，我们建议在仔细分型的MTOPS组织库中测试这三种标志物，其中可以进行与前列腺大小、生长速率、症状进展和对治疗的反应的详细相关性。 此外，我们建议探索一种独特的信号通路（DOC-2）的潜在作用，我们认为它是前列腺干细胞增殖的重要标志物，以及端粒酶表达在前列腺癌发展中的BPH进展中的潜在作用。

DESCRIPTION (provided by applicant): UT Southwestern Prostate Disease Center investigators have worked together for more than a decade to study the pathogenesis of benign prostatic hyperplasia (BPH) from basic, translational and clinical research prospectives. Our investigators provided the major leadership for the design, supervision and conduct of the NIDDKK-funded MTOPS trial. Furthermore, the group has developed a substantial amount of preliminary data demonstrating the role of several biomarkers in the progression of BPH. Based upon this preliminary evidence, we propose to specifically validate the following biomarkers (or biomarker families) as markers of BPH progression: the prostatic smooth muscle contractile protein phenotype, prostatic alpha-2 macroglobulin, and type 2 5a-reductase. Further assay optimization will be performed with these three biomarkers using the UT Southwestern NIDDK-funded George W. O'Brien Tissue Repository, which contains more than 600 BPH samples and appropriate controls. After assay validation, we propose to test these three markers in the carefully phenotyped MTOPS tissue bank, where detailed correlation with prostate size, growth rate, symptomatic progression and response to therapy can be performed. Furthermore, we propose to explore the potential role of a unique signaling pathway (DOC-2) we believe is an important marker for stem cell proliferation in the prostate, as well as the potential role of telomerase expression in BPH progression in the development of prostatic cancer.