MTOPS Biomarker Unit at the University of Pittsburgh

描述(由申请人提供)： 良性前列腺增生症(BPH)是一种病因不明的疾病，严重影响老年男性的生活质量。组织学上的良性前列腺增生症可表现为有症状或无症状。为了阐明BPH背后的分子差异，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了症状性和非症状性BPH。这种遗传特征将BPH与正常组织区分开来，但似乎不会随着年龄的增长而改变。这一分析导致了几个靶点的确定，这些靶点似乎将BPH与有症状的人和组织学上的BPH区分开来。作为MTOPS前列腺样本分析联盟的生物标记物单位，我们建议以合作的性质利用这些标记物来分析作为前列腺症状医学治疗临床试验的一部分收集的组织和血清样本。我们的生物标记单位将与现有的MTOPS数据协调中心、病理协调中心以及其他获奖的生物标记单位密切合作。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一部分获得的临床参数相关。这一假设将通过以下具体目标来解决：1)分析从MTOPS试验获得的活检样本以及本库正常和无症状的BPH(有症状和无症状)组织中JM-27、BMP-5(列出其他标记物)以及其他标记物的表达，并将上述标记物与治疗反应和症状进展相关联；2)建立基于血清的方法以检测上述标记物在MTOPS试验以及本研究所的正常和BPH(有症状和无症状)患者样本中的表达；以及3)进一步开发一种系统，通过该系统可以分析MTOPS联盟开发的其他标记并确定其优先顺序。作为MTOPS联盟的一个组成部分，这些研究应该为开发新的生物标记物提供有用的诊断和特征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.