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裔美国人男性的不成比例的影响。我们方法学的指导原则是非裔美国人和欧洲美国人起源的前列腺癌之间存在生化差异，这些差异可以部分解释前列腺癌健康差异。在这项应用中，我们建议使用代谢组谱技术来揭示这些潜在的差异。代谢组学描述了一门量化代谢物(例如，小分子)水平的科学，这些代谢物是 细胞新陈代谢。也就是说，在这种分析中，我们测量的是由细胞功能机械产生的生化实体(或代谢物)。通过了解特定代谢物的特性，我们可以推断产生这些代谢物的生物过程，从而深入了解细胞的新陈代谢。到目前为止，还没有关于前列腺癌健康差异的代谢分析的报道。在初步研究中，我们分析了非裔美国人和欧洲裔美国人前列腺癌的代谢组，并确定了特定的种族差异代谢物以及与每种代谢物相关的生物途径。在这项提案中，我们将i)验证和完善非裔美国人和欧洲裔美国人前列腺癌的代谢图谱，ii)评估特定生化途径在非裔美国人和欧洲裔美国人前列腺癌中的作用，以及iii)开发基于尿液的代谢标记物，用于非洲裔美国人和欧洲裔美国人男性的高危前列腺癌。在这项研究的结论中，我们将开发出前列腺癌的种族来源代谢组学模型，并确定了未来药物靶向的候选途径。

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.