MTOPS Biomarker Unit at the University of Pittsburgh

描述（由申请人提供）： 良性前列腺增生（BPH）是一种病因不明的疾病，严重影响老年男性的生活质量。组织学上的BPH可以表现为症状性或无症状性。为了阐明BPH的分子差异，使用微阵列分析了前列腺移行区组织的基因表达谱。一组511个差异表达基因区分有症状和无症状的BPH。这种基因特征将BPH与正常组织分开，但似乎不会随年龄而改变。这种分析导致了几个目标的识别，这似乎是区分BPH的个人与组织学BPH的症状。作为MTOPS前列腺样本分析联盟的生物标志物单位，我们建议以合作的方式利用这些标志物来分析作为前列腺症状药物治疗临床试验的一部分收集的组织和血清样本。我们的生物标志物部门将与现有的MTOPS数据协调中心、病理学协调中心以及其他获奖的生物标志物部门密切合作。我们假设，我们已经确定的遗传标记可能与BPH的发生以及BPH的严重程度、对药物的反应以及作为研究的一部分获得的临床参数相关。本研究将通过以下几个方面的研究来验证这一假说：1）分析JM-27、BMP-5在人乳腺癌组织中的表达，（列出其他标志物）以及从MTOPS试验获得的活检样品中的其他标志物以及正常和BPH（有症状的和无症状的）组织，并将上述标志物与对治疗的反应和症状进展相关联; 2）开发基于血清的方法，用于测试从MTOPS试验获得的患者样品以及从我们机构获得的正常和BPH（有症状和无症状）个体中的上述标志物的表达;以及3）进一步开发系统，通过该系统可以分析由MTOPS联盟开发和优先化的其他标志物。作为MTOPS联盟的一部分，这些研究应该提供新的生物标志物的开发，用于诊断和表征BPH。

DESCRIPTION (provided by applicant): Benign Prostatic Hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not appear to change with age. This analysis resulted in the identification of several targets, which appear to differentiate BPH from individuals with symptoms from those with histologic BPH. As a Biomarker Unit of the MTOPS Prostate Sample Analysis Consortium we propose to both utilize these markers in a cooperative nature to analyze the tissue and serum samples collected as part of the Medical Therapy of Prostatic Symptoms clinical trial. Our Biomarker Unit will work closely together with the existing MTOPS Data Coordinating Center, the Pathology Coordinating Center as well as the other awarded Biomarker Units. We hypothesize that the genetic markers that we have identified may correlate with the occurrence of BPH as well as the severity of the BPH, responses to pharmacological agents as well as with clinical parameters obtained as part of the study. This hypothesis will be addressed by conducting the following specific aims: 1) to analyze the expression of JM-27, BMP-5 (list other markers) as well as other markers in biopsy samples obtained from the MTOPS trial as well as normal and BPH (symptomatic and asymptomatic) tissues in our bank and to correlate the above-described markers with both response to therapy and symptom progression ; 2) to develop serum-based methodologies for testing the expression of the above-described markers in patient samples obtained from the MTOPS trial as well as from normal and BPH (symptomatic and asymptomatic) individuals from our Institution; and 3) to further develop a system by which other markers developed and prioritized by the MTOPS Consortium can be analyzed. As a component of the MTOPS Consortium, these studies should provide the development of novel biomarkers with utility in diagnosing and characterizing BPH.