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

与欧洲膀胱癌相比，非裔美国人膀胱癌的种族差异以及代谢改变的鉴定

• 批准号: 9388440
• 负责人: Nagireddy Putluri
• 金额: $ 37.07万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-05 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9388440
• 关键词: Accounting; Acetylation; Acetyltransferase; Address; African American; Alcohol dehydrogenase; American; Aspartic Acid; Bioenergetics; Biological; Biological Factors; Biological Markers; Cancer Patient; Cancer cell line; Caring; Clinical; Cystectomy; Data; Development; Diagnostic; Disease; Disease Outcome; Disease Progression; Enzymes; European; Generations; Genes; Genetic; Glean; Glioma; Glutaminase; Glutamine; Hypermethylation; In Vitro; Incidence; Iron; Isocitrate Dehydrogenase; Label; Lipids; Malignant neoplasm of urinary bladder; Marital Status; Mass Spectrum Analysis; Measurement; Measures; Messenger RNA; Metabolic; Metabolic Marker; Metabolic Pathway; Metabolism; Methodology; Mitochondria; Muscle; Mutation; NAT1 gene; Occupational Exposure; Oncogenic; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Pharmaceutical Preparations; Pharmacology; Phospholipase A1; Phosphorylcholine; Pilot Projects; Positioning Attribute; Proteins; Publications; Publishing; Race; Reporting; Research; Role; SEER Program; Seminal; Smoker; Smoking; Socioeconomic Factors; Techniques; Therapeutic; Tissues; Urine; Xenobiotic Metabolism; Xenograft procedure; base; cancer health disparity; combinatorial; experience; glutaric acid; health care availability; health disparity; in vivo; inhibitor/antagonist; lecithin-retinol acyltransferase; lipid metabolism; metabolome; metabolomics; mitochondrial metabolism; mortality; prognostic; racial disparity; racial health disparity; therapeutic target; treatment strategy; triple-negative invasive breast carcinoma; tumor; tumor progression

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.

项目概要/摘要 据了解，非洲裔美国患者的膀胱癌 (BCa) 死亡率较高。存在差距 非洲裔美国人 (AA) 和欧洲裔美国人 (EA) 在 BCa 临床结果方面的差异。长期来看 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的影响 美国人。我们方法的指导原则是线粒体代谢物的改变存在于 非裔美国人和欧洲裔美国人的 BCa，这些差异可以部分解释 BCa 的健康状况 差距。在此应用中，我们建议使用代谢组学分析技术来揭示这些 根本差异。迄今为止，旨在了解膀胱癌健康状况的代谢组学分析 差异尚未被报道。我们最近发表了第一篇描述代谢改变的研究 与膀胱癌有关。在初步研究中，我们分析了 AA 和 BCa 的代谢组 EA 患者并确定了线粒体代谢物和脂质中独特的 AA 种族特异性表达模式。 在本提案中，我们将 i) 描述 AA 和 EA BCa 中线粒体相关代谢物的特征，ii) 验证 BCa 患者中的 D-2HG 和相关酶（GLS、ADHFE1 和 IDH1/2）并建立 AA BCa 中谷氨酰胺代谢的治疗靶向失调途径 iii) 评估溶血水平 PC和PC及其代谢酶PLA1A和LRAT在AA BCa中的功能。成功者 拟议研究的完成将对膀胱癌健康差异领域产生重大影响 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代谢 BCa 的标志物和治疗靶点。总而言之，从该提案中收集的信息可以 通过揭示生物学原理，迅速彻底改变当前的诊断、预后和治疗方法 膀胱癌健康差异的基础。