Project 1-Vanderbilt Developmental Center for Translational Research in Benign Urologic Diseases

项目概要-项目01 导致良性前列腺增生（BPH）的下尿路症状（LUTS）的复杂性， 符合一些条件，其中一些可能是因果关系的疾病状态，而其他可能是一个 共同病理生理变化的结果。这种复杂的病因使治疗复杂化， 对标准治疗（包括5α-还原酶抑制剂）无应答或产生耐药性的患者 （5ARI）或α-肾上腺素能阻滞剂（α-阻滞剂）。该中心的首要目标是开发一个新的 研究和培训资源的研究社区调查BPH病理生理学和药物 治疗失败该资源开发项目将利用来自医学治疗的组织和数据， 前列腺症状（MTOPS）开发和传播扩展BPH研究的基因表达数据。 MTOPS将患有LUTS的男性随机分配至5ARI、α受体阻滞剂、5ARI+ α受体阻滞剂联合治疗或安慰剂组，以及 前瞻性随访参与者的BPH进展。在目标1中，我们对过渡区进行了RNA测序， 在基线和随访时收集的BPH进展男性（n=98）的前列腺组织， 治疗后无BPH进展的受试者的封闭随机样本（n=98）。新资源将 为社区提供必要的数据，以确定基因，基因集和与之相关的途径。 LUTS严重程度、LUTS严重程度的变化和对治疗的耐药性。在目标2中：我们创建一个Web界面 这样研究者可以了解数据源，进行初始查询，并获得基因表达 数据来测试BPH的新假设。这个资源开发项目将利用我们的经验， 实验室分析、数据管理、生物统计学和生物信息学分析，以创建RNA-Seq 来自MTOPS人类BPH组织库的基因表达文库和传播平台。没有 在BPH/LUTS患者中前瞻性重复采集组织， 治疗后我们对该中心的愿景是，开发的资源将为调查人员打开大门， 包括初级研究人员，以有效地测试新的想法，并加快探索新的假设， BPH病理生理学和治疗反应/失败。

Project Summary – Project 01 The complexity of lower urinary tract symptoms (LUTS) leading to benign prostatic hyperplasia (BPH) can coincide with a number of conditions, some of which may be causal to the disease state while others may be a consequence of shared pathophysiologic changes. This complex etiology complicates treatment, with many patients non-responsive or developing resistance to standard therapies including 5α-reductase inhibitors (5ARI) or alpha-adrenergic blockers (alpha-blockers). The overarching goal of this Center is to develop a new resource for research and training for the research community to investigate BPH pathophysiology and drug therapy failure. This Resource Development Project will utilize tissue and data from the Medical Therapy of Prostatic Symptoms (MTOPS) to develop and disseminate gene expression data for extended BPH research. MTOPS randomized men with LUTS to a 5ARI, alpha-blocker, combined 5ARI+alpha blocker, or placebo, and prospectively followed participants for BPH progression. In Aim 1, we conduct RNA-Seq on transitional zone prostate tissue collected at baseline and follow-up among those men with BPH progression (n=98) and a blocked random sample of participants without BPH progression after treatment (n=98). This new resource will provide the community with the data necessary to identify genes, gene sets, and pathways associated with LUTS severity, change in LUTS severity, and resistance to treatment. In Aim 2: we create a web-interface such that investigators may learn about the data resource, conduct initial queries, and obtain gene expression data to test new hypotheses of BPH. This Resource Development Project will utilize our experience in laboratory analyses, data management, and biostatistical and bioinformatic analyses to create the RNA-Seq gene expression library and dissemination platform from the MTOPS human BPH tissue repository. No comparable resource exists with prospectively repeated tissue collection within BPH/LUTS patients before and after treatment. Our vision for this Center is that the resources developed will open the doors for investigators, including junior investigators, to efficiently test new ideas and accelerate the exploration of novel hypotheses of BPH pathophysiology and treatment response/failure.