METABOLOMIC PROFILING AND BIOLOGIC BASIS OF RACIAL DISPARITY IN PROSTATE CANCER

描述（由申请人提供）：我们研究计划的长期目标是减少前列腺癌对非洲裔美国男性的不成比例的影响。我们方法的指导原则是非裔美国人和欧洲裔美国人起源的前列腺癌之间存在生物化学差异，这些差异可以部分解释前列腺癌健康差异。在本申请中，我们建议使用代谢组学分析技术来揭示这些潜在的差异。代谢组学描述了定量代谢物水平的科学（例如，小分子）的副产品 细胞代谢也就是说，在这种分析中，我们测量的是由细胞功能机制产生的生化实体（或代谢物）。通过了解特定代谢物的身份，我们可以推断产生它们的生物过程，从而深入了解细胞的代谢。迄今为止，尚未报道前列腺癌健康差异的代谢组学分析。在初步研究中，我们已经分析了非洲裔美国人和欧洲裔美国人男性前列腺癌的代谢组，并确定了特定的种族不同的代谢物以及与每种代谢物相关的生物学途径。在本提案中，我们将i）验证和完善非洲裔美国人和欧洲裔美国人男性前列腺癌的代谢组学特征，ii）评价特定生化途径在非洲裔美国人和欧洲裔美国人男性前列腺癌中的作用，iii）开发非洲裔美国人和欧洲裔美国人男性高危前列腺癌的尿液代谢标志物。在这项研究的结论，我们将开发一个种族衍生的代谢组学模型，前列腺癌以及确定候选途径，为未来的药物靶向。

DESCRIPTION (provided by applicant): The long-term objective of our research plan is to reduce the disproportionate effects of prostate cancer on African American men. A guiding principle of our methodology is biochemical differences exist between prostate cancers of African American and European American origin and that these differences can explain, in part, prostate cancer health disparity. In this application, we propose to use the technique of metabolomic profiling to uncover these underlying differences. Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules) that are the byproducts of cellular metabolism. That is to say, in this kind of analysis we are measuring the biochemical entities (or metabolites) that are produced by the functional machinery of the cell. With knowledge of the identity of specific metabolites we can infer the biological processes that produced them, thus gaining insight into a cell's metabolism. To date, a metabolomic analysis of prostate cancer health disparity has not been reported. In preliminary studies, we have profiled the metabolome of prostate cancers from African-American and European American men and have identified specific racially distinct metabololites as well as biological pathways associated with each. In this proposal, we will i) validate and refine the metabolomic profile of prostate cancers from African American and European American men, ii) evaluate the role of specific biochemical pathways in prostate cancers of African American and European American men and iii) develop urine based metabolic markers for high risk prostate cancer in African American and European American men. At the conclusion of this study, we will have developed a racially derived metabolomic model for prostate cancer as well as identified candidate pathways for future drug targeting.