Metabolomic discovery and validation of urinary biomarkers for kidney cancer

肾癌尿液生物标志物的代谢组学发现和验证

• 批准号: 8433239
• 负责人: ROBERT H. WEISS
• 金额: $ 29.14万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-23 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433239
• 关键词: African American; Area; Biological Assay; Biological Markers; Cancer Patient; Cause of Death; Cell Line; Cells; Chemicals; Clinic; Collaborations; Collection; Conventional (Clear Cell) Renal Cell Carcinoma; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Discrimination; Disease; Early Diagnosis; Enrollment; Future; Genomics; Glean; Grant; Health; Hematuria; Imaging Techniques; Incidence; Individual; Information Networks; Institution; Kidney; Kidney Diseases; Laboratories; Lead; Malignant Neoplasms; Metabolic; Metabolic Pathway; Methods; Microscopic; Modeling; Molecular; Monitor; Non-Malignant; Oncogenic; Oncologist; Pathogenesis; Pathologist; Pathway Analysis; Pathway interactions; Patient Monitoring; Patients; Pattern; Primary Health Care; Proteins; Proteomics; Publications; Renal Cell Carcinoma; Renal carcinoma; Sampling; Science; Scientist; Signal Pathway; Smoker; Solid; Staging; Symptoms; Technology; Testing; Time; Tissues; Training; Treatment Protocols; Urine; Validation; Work; Writing; base; chemotherapy; clinical material; computerized tools; design; high risk; improved; in vivo; metabolomics; novel; research study; response; sound; statistics; tool; tumorigenesis; urinary; urologic

DESCRIPTION (provided by applicant): Kidney cancer (also known as renal cell carcinoma [RCC]) is diagnosed in 36,000 patients and is the cause of death of 11-13,000 individuals yearly in the US; unfortunately (and for unknown reasons), the incidence of this disease is increasing in all groups. One-third of cases, many of whom are asymptomatic, are metastatic at diagnosis and there is currently no available biofluid diagnostic test or adequate treatment once diagnosed. Given the relationship of the kidney to the urine, RCC is ideally suited for identification of urinary markers. In this revised proposal, we will exploit the new science of metabolomics to discover a pattern of urinary metabolites which serve as biomarkers for RCC in patients who are at high risk for this disease. We will support our biomarkers discovery by using pathway and network analysis to confirm which metabolic pathways go awry in this disease, using RCC tissues and cell lines. Finally, we will test our biomarkers in new samples from both RCC non-RCC patients, including as controls patients with non-malignant renal disease as well as patients who have non-renal cancers. For this revision, we have improved the proposal by adding all of the requested preliminary data. We have also submitted two publications related to RCC metabolomics as well as proteomics. Our proposal is extraordinary in that we have assembled a unique cadre of collaborators: a cell biologist who is also a clinician- scientist nephrologist (Dr. Weiss), a proteomics and genomics expert (Dr. Perroud), four metabolomics experts (Drs Fiehn, Hammock, Michelmore, and Grant), two biostatisticians (Drs. Kim and Rocke), two oncologic pathologists (Drs. Grizzle and Borowsky), and two urologic oncologists (Drs. De Vere White and Evans) to utilize metabolomics to tackle the problem of diagnosis and treatment of a cancer which is difficult to diagnose, whose incidence is increasing, and for which current treatment options are dismal. We are pleased that the reviewers agreed that the experiments in our proposal were sound. Successful completion of these experiments will result in a major advance in diagnosis as well as, ultimately, the selection of optimal treatment regimens for this disease. Ours will be the first described use of this technology in urologic malignancy, and one of the first to exploit this technology in any cancer. Furthermore, our work can serve as a model for using metabolomics to glean oncogenic pathway and network data from a variety of cancers.

描述（由申请人提供）：肾癌（也称为肾细胞癌[RCC]）在36，000名患者中被诊断出来，并且是美国每年11- 13，000人死亡的原因;不幸的是（并且由于未知原因），该疾病的发病率在所有组中都在增加。三分之一的病例，其中许多是无症状的，在诊断时是转移性的，目前没有可用的生物流体诊断测试或诊断后的适当治疗。考虑到肾脏与尿液的关系，RCC非常适合用于识别尿液标记物。在这个修订后的提案中，我们将利用代谢组学的新科学来发现尿代谢物的模式，这些模式可以作为这种疾病高风险患者的RCC的生物标志物。我们将通过使用途径和网络分析来支持我们的生物标志物发现，以确认哪些代谢途径在这种疾病中出错，使用RCC组织和细胞系。最后，我们将在来自RCC非RCC患者的新样本中测试我们的生物标志物，包括作为对照的非恶性肾病患者以及非肾癌患者。对于本次修订，我们通过添加所有要求的初步数据来改进提案。我们还提交了两份与RCC代谢组学和蛋白质组学相关的出版物。我们的建议是非凡的，因为我们已经聚集了一个独特的合作者骨干：他是一位细胞生物学家，同时也是一位临床科学家，（韦斯博士），蛋白质组学和基因组学专家（Perroud博士），四位代谢组学专家（Fiehn、Hammock、Michelmore和Grant博士），两位生物统计学家（Kim和Rocke博士），两位肿瘤病理学家（Grizzle和Borowsky博士），和两名泌尿肿瘤学家（Drs. De Vere白色和Evans）利用代谢组学来解决难以诊断的癌症的诊断和治疗问题，其发病率正在增加，而目前的治疗方案也很糟糕。我们感到高兴的是，审查人员同意我们提案中的实验是合理的。这些实验的成功完成将导致诊断的重大进展，并最终为这种疾病选择最佳治疗方案。我们将是第一个描述使用这项技术在泌尿系统恶性肿瘤，并首先利用这项技术在任何癌症之一。此外，我们的工作可以作为一个模型，使用代谢组学收集致癌途径和网络数据从各种癌症。