Metabolomics-based Identification of Hepatocellular Cancer Biomarkers

基于代谢组学的肝细胞癌生物标志物鉴定

• 批准号: 7740257
• 负责人: MARY Alice MALUCCIO
• 金额: $ 21.15万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-17 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740257
• 关键词: Accounting; Basic Science; Biochemical; Biological; Biological Markers; Blinded; Blood; Blood Screening; Cancer Patient; Caring; Cellular Stress; Chemicals; Chronic Active Hepatitis; Cirrhosis; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Early treatment; Foundations; Goals; Hepatitis; Hepatitis C; Individual; Interdisciplinary Study; Knowledge; Link; Liver; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Mass Spectrum Analysis; Measurement; Measures; Medical Oncologist; Metabolic; Metabolic Marker; Metabolism; Methods; Molecular Weight; Mutation; NMR Spectroscopy; Non-Malignant; Nuclear Magnetic Resonance; Patients; Primary carcinoma of the liver cells; Relative (related person); Research Proposals; Resources; Risk Assessment; Sampling; Scientific Advances and Accomplishments; Screening for Hepatocellular Cancer; Sensitivity and Specificity; Serum; Signal Transduction; Statistical Methods; Statistical Models; TOCSY; Techniques; Testing; Tissues; Translating; Tumor Tissue; Validation; Variant; Work; alpha-Fetoproteins; base; cancer diagnosis; cancer risk; clinical application; clinical practice; disease diagnosis; early onset; health care delivery; high risk; human tissue; liver function; metabolomics; mortality; outcome forecast; public health relevance; research study; small molecule; tool

DESCRIPTION (provided by applicant): The proposed work focuses on the discovery of reliable biomarkers for the early detection of liver cancer. Patients with hepatitis are particularly susceptible to the development of hepatocellular cancer, although the disease mechanisms are poorly understood. We propose to use metabolomics, an emerging field that provides new information on biological perturbations based on changes in multiple small molecule metabolites. New advances in nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) and their combination with multivariate statistical methods provide a promising approach for early disease diagnosis and for following therapy. Presently, no highly reliable metabolite biomarkers have been identified that are early indicators of the presence of liver cancer. Our aim is to identify key metabolic signatures that may be diagnostic of the early onset of the disease, thus opening up the possibility for earlier therapy, and thereby reducing overall mortality rates. Detection of liver cancer using metabolomics will be based on the establishment of key small molecular weight metabolite signatures in serum and tissue from human patients, as well as serum samples from patients with non-malignant liver disease and healthy controls using advanced NMR/MS techniques. A putative set of biomarker candidates from serum have already been identified from a moderate number of patient samples. Correlation of signals from tumor tissue and serum will help identify additional key metabolic signatures in serum that may be used to detect early liver cancer non-invasively. Validation of a statistical model based on these metabolic markers will be performed on a set of blinded samples. If successful, this advance would provide medical oncologists with the new tools and knowledge to more efficiently care for liver cancer patients. This project will lay the foundation for clinical applications of metabolomics of early liver cancer diagnosis on a large number of patients, while advancing scientific knowledge on disease mechanisms through basic research. This approach could then very quickly be translated into clinical practice. PUBLIC HEALTH RELEVANCE: This project seeks to develop a new and non-invasive method for early liver cancer detection by identifying small molecules in the blood that indicate the onset of cancer, especially for patients with hepatitis.

描述（由申请人提供）：拟议的工作重点是发现可靠的生物标志物，用于肝癌的早期检测。肝炎患者特别容易发生肝细胞癌，尽管对疾病机制知之甚少。我们建议使用代谢组学，这是一个新兴领域，提供了基于多种小分子代谢物变化的生物扰动的新信息。核磁共振（NMR）光谱和质谱（MS）的新进展及其与多元统计方法的结合为早期疾病诊断和后续治疗提供了一种有前途的方法。目前，还没有高度可靠的代谢物生物标志物被确定为肝癌存在的早期指标。我们的目标是确定可能诊断该疾病早期发作的关键代谢特征，从而为早期治疗提供可能性，从而降低总体死亡率。使用代谢组学检测肝癌将基于使用先进的NMR/MS技术在来自人类患者的血清和组织以及来自非恶性肝病患者和健康对照的血清样本中建立关键的小分子量代谢物特征。已经从中等数量的患者样品中鉴定了来自血清的一组推定的生物标志物候选物。来自肿瘤组织和血清的信号的相关性将有助于识别血清中的其他关键代谢特征，这些特征可用于非侵入性地检测早期肝癌。将对一组设盲样本进行基于这些代谢标志物的统计模型验证。如果成功，这一进展将为医学肿瘤学家提供新的工具和知识，以更有效地治疗肝癌患者。该项目将为代谢组学在肝癌早期诊断中的大量临床应用奠定基础，同时通过基础研究推进对疾病机制的科学认识。这种方法可以很快地转化为临床实践。 公共卫生关系：该项目旨在开发一种新的非侵入性早期肝癌检测方法，通过识别血液中指示癌症发作的小分子，特别是对于肝炎患者。