METABOLOMIC PROFILING AND BIOLOGIC BASIS OF RACIAL DISPARITY IN PROSTATE CANCER

前列腺癌种族差异的代谢组学分析和生物学基础

基本信息

批准号：
8716699
负责人：
Ganesh S Palapattu
金额：
$ 31.44万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8716699
关键词：
Affect African American American Benign Biochemical Biochemical Pathway Bioinformatics Biological Biological Assay Biological Markers Biological Process Biology Body Fluids Case-Control Studies Cell physiology Cells Clinical Management Complex Cyclic Nucleotides Data Data Set Diagnostic Disease Drug Targeting Environmental Health European Future Gene Proteins Genes Genetic Genomics Glean Gleason Grade for Prostate Cancer Goals Health Services Accessibility Healthcare Human In Vitro Incidence Inequality Knowledge Liquid substance Malignant Neoplasms Malignant neoplasm of prostate Mass Spectrum Analysis Measures Metabolic Marker Metabolic Pathway Metabolism Methodology Modeling Molecular Conformation Names Outcome Output PC3 cell line Pathology Pathway interactions Phenotype Play Poly(ADP-ribose) Polymerases Pre-Clinical Model Process Property Proteins Proteomics Reporting Research Risk Role Sarcosine Science Signal Transduction Specimen Techniques Testing Therapeutic Time Tissues Transcript Urine arm base cancer health disparity cancer statistics health disparity high risk improved in vivo insight men metabolomics novel nucleotide metabolism prognostic prostate cancer model small molecule sobriety transcriptomics tumor progression urinary

项目摘要

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.

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男性的不成比例的影响。我们方法的指导原则是非洲裔美国人和欧洲裔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的健康差异。在此应用中，我们建议使用代谢组学分析技术来揭示这些潜在差异。代谢组学描述了量化代谢物（例如小分子）水平的科学，这些代谢物是代谢物的副产品。细胞代谢。也就是说，在这种分析中，我们测量的是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新陈代谢。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，我们分析了非裔美国人和欧洲裔美国男性前列腺癌的代谢组，并确定了特定种族不同的代谢物以及与每种代谢物相关的生物途径。在本提案中，我们将 i) 验证和完善非裔美国人和欧洲裔美国男性前列腺癌的代谢组学特征，ii) 评估特定生化途径在非裔美国人和欧洲裔美国男性前列腺癌中的作用，以及 iii) 开发基于尿液的方法非裔美国人和欧洲裔美国男性高风险前列腺癌的代谢标志物。在这项研究结束时，我们将开发出一种针对前列腺癌的种族衍生代谢组学模型，并确定未来药物靶向的候选途径。