Racial Disparity in Bladder Cancer and Identification of Altered Metabolism in African American Compare to European Bladder Cancer

项目摘要/摘要 它已经知道，非裔美国人的膀胱癌(BCA)死亡率更高。贫富差距存在 在BCA的临床结局中，非裔美国人(AA)和欧洲裔美国人(EA)之间的差异。长期的 我们研究计划的目标是减少膀胱癌(BCA)对非洲人的不成比例影响 美国人。我们方法学的指导原则是线粒体代谢物的改变存在于 非洲裔美国人和欧洲裔美国人的BCA，这些差异可以部分解释BCA的健康 贫富差距。在这个应用中，我们建议使用代谢组谱技术来揭示这些 潜在的差异。迄今为止，一项旨在了解膀胱癌健康状况的代谢分析 目前还没有关于差异的报道。我们最近发表了第一项描述代谢变化的研究 与膀胱癌有关。在初步研究中，我们已经描绘了来自AA和BCA的代谢组 EA患者，并在线粒体代谢物和脂类中发现了明显的AA小种特异性表达模式。 在这个方案中，我们将：i)表征AA和EA BCA中的线粒体相关代谢物，ii)验证 BCA患者D-2HG及其相关酶(GLS、ADHFE1和IDH1/2)的检测 针对AA患者谷氨酰胺代谢的治疗靶向性去调节途径III)评估溶血素水平 PC和PC及其代谢酶PLA1A和LRAT在AA BCA中的作用。成功者 拟议研究的完成将对膀胱癌健康差距领域产生重大影响 和新陈代谢。重要的是，我们的研究结果有可能揭示种族排斥的新陈代谢 BCA的标志物和治疗靶点。综上所述，从这项提案中收集的信息可能 通过揭示生物学特征，迅速革新当前的诊断、预测和治疗方法 膀胱癌健康差异的基础。

Project Summary/Abstract It has known that bladder cancer (BCa) mortality is higher in African American patients. Disparity exists between African-American (AA) and European-American (EA), in the clinical outcome of BCa. The long-term objective of our research plan is to reduce the disproportionate effects of bladder cancer (BCa) on African American. A guiding principle of our methodology is that alterations in mitochondrial metabolites exist between African American and European American BCa and that these differences can explain, in part, BCa health disparity. In this application, we propose to use the technique of metabolomic profiling to uncover these underlying differences. To date, a metabolomic analyses aimed at understanding of bladder cancer health disparity has not been reported. We have recently published the first study describing metabolic alterations associated with bladder cancer. In preliminary studies, we have profiled the metabolome of BCa from AA and EA patients and identified a distinct AA race-specific expression pattern in mitochondrial metabolites and lipids. In this proposal, we will i) characterize the mitochondrial associated metabolites in AA and EA BCa, ii) verify the D-2HG and associated enzymes (GLS, ADHFE1, and IDH1/2) in BCa patients and establish a therapeutically targeted deregulation pathway for glutamine metabolism in AA BCa iii) assess the levels of lyso PC and PC and the function of their metabolizing enzymes PLA1A and LRAT in AA BCa. The successful completion of the proposed studies will have a significant impact in the field of Bladder cancer health disparity and metabolism. Importantly, findings from our study have the potential to reveal racially exclusive metabolic markers and therapeutic targets for BCa. Taken together, the information gleaned from this proposal could rapidly revolutionize current diagnostic, prognostic and therapeutic approaches by revealing the biological underpinnings of bladder cancer health disparity.