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

• 批准号: 8857576
• 负责人: Ganesh S Palapattu
• 金额: $ 10.04万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/8857576
• 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

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）：我们的研究计划的长期目标是减少前列腺癌对非裔美国人的不成比例影响。我们方法论的指导原则是非洲裔美国和欧美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。在此应用程序中，我们建议使用代谢组分析的技术来发现这些潜在的差异。代谢组学描述了量化代谢产物水平（例如，小分子）的科学，这些水平是 细胞代谢。也就是说，在这种分析中，我们正在测量由细胞功能机械产生的生化实体（或代谢产物）。了解特定代谢物的身份，我们可以推断产生它们的生物学过程，从而深入了解细胞的代谢。迄今为止，尚未报道对前列腺癌健康差异的代谢组分分析。在初步研究中，我们介绍了来自非裔美国人和欧美男人的前列腺癌的代谢组，并确定了特定的种族不同的代谢产物以及与每个人相关的生物学途径。在此提案中，我们将验证和完善来自非洲裔美国人和欧美男人的前列腺癌的代谢组概况，ii）评估特定生物化学途径在非洲裔美国人和欧美男人和iii的前列腺癌中的作用），发展为非裔美国人和欧洲裔美国人的高风险前列腺癌的代谢标记。在这项研究的结论中，我们将开发出一种种族衍生的前列腺癌代谢组模型，并确定了未来药物靶向的候选途径。