Metabolomic and Integromic Approaches to Identify Fingerprints for Early Detectio

识别指纹以进行早期检测的代谢组学和整合组学方法

• 批准号: 7993637
• 负责人: Habtom W Ressom
• 金额: $ 20.03万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993637
• 关键词: Address; Algorithms; Biochemistry; Bioinformatics; Biological; Biological Markers; Biomedical Research; Biometry; Cancer Biology; Cells; Chronic; Cirrhosis; Clinical; Complex; Coupled; Data; Databases; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Management; Disease Progression; Early Diagnosis; Fingerprint; Health; Heterogeneity; Human; Individual; Ions; Knowledge; Laboratories; Liquid Chromatography; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Mass Spectrum Analysis; Metabolic; Metabolic Marker; Modeling; Molecular; Molecular Profiling; Newly Diagnosed; Organism; Outcome; Outcome Study; Pathway interactions; Patients; Peptides; Performance; Peripheral; Phenotype; Plasma; Polysaccharides; Population; Primary carcinoma of the liver cells; Proteomics; Sampling; Screening procedure; Signal Pathway; Staging; Statistical Methods; Testing; Time; University Hospitals; anticancer research; candidate validation; design; drug development; drug metabolism; high risk; improved; mass spectrometer; metabolomics; multiple reaction monitoring; new therapeutic target; novel; public health relevance; small molecule; tandem mass spectrometry; therapeutic development; treatment strategy

DESCRIPTION (provided by applicant): The accumulation of omics data at multiple levels provides an opportunity to better understand the progression of chronic liver disease (CLD) to hepatocellular carcinoma (HCC). A variety of HCC- associated molecular alterations have been detected. However, due to the lack of good diagnostic markers and treatment strategies, and because of the disease heterogeneity in human populations, a coherent understanding of the mechanism of HCC development is still limited. The assessment of complex multigenic molecular pathways in HCC remains a difficult challenge. This project brings together experts in bioinformatics, biostatistics, biochemistry, clinical cancer research, and mass spectrometry to EM Algorithm, Posterior Mode</keyword></keywords><dat treatment of HCC. Specifically, this project Evaluate metabolic changes in the progression of CLD to HCC in serum and plasma samples by an ultra-performance liquid chromatography coupled with a quadrupole time of flight mass spectrometry (UPLC-QTOF MS). Serum and plasma samples collected from newly diagnosed HCC cases and matched cirrhotic controls will be utilized. The identified metabolic biomarkers will be verified by comparing their tandem mass spectrometry data with those generated from commercially available standard compounds. (2) Investigate key metabolic and signaling pathways that may be altered in the progression of CLD to HCC. Specifically, we will utilize a pathway-centric approach by integrating experimental findings from multiple studies, including our previous proteomics and glycomics studies, to provide a "molecular map" of changes in HCC to aid in the design of targets for diagnostic and therapeutic development. We anticipate the outcome of this study to enhance our understanding of the disease progression and the functional involvement of candidate HCC biomarkers in metabolic and signaling pathways. PUBLIC HEALTH RELEVANCE: Defining clinically applicable biomarkers that detect early-stage hepatocellular carcinoma (HCC) in a high-risk population of cirrhotic patients has potentially far-reaching consequences for disease management and patient health. This project is important because most HCC patients are diagnosed at a late stage, where the treatment options are limited. There is a pressing need to identify biomarkers that could be used for early detection of HCC. This project will capitalize on markers identified in this and other studies to investigate fingerprints that may be related to the progression of HCC. In addition to screening high-risk populations for early signs of disease, the identified biomarkers and knowledge of their functional involvement in metabolic and signaling pathways could be used to design and test improved treatment strategies.

描述(由申请人提供)：多层次组学数据的积累为更好地了解慢性肝病(CLD)到肝细胞癌(HCC)的进展提供了机会。已检测到多种与肝细胞癌相关的分子改变。然而，由于缺乏良好的诊断标记物和治疗策略，以及人类群体中疾病的异质性，对肝癌发生机制的一致理解仍然有限。对复杂的多基因分子通路在肝细胞癌中的评估仍然是一个困难的挑战。这个项目汇集了生物信息学、生物统计学、生物化学、临床癌症研究和质谱学方面的专家，以EM算法、后验模式/关键字和关键字&lt；/关键字&>dat；治疗肝癌。具体地说，该项目使用超高效液相色谱结合四极杆飞行时间质谱仪(UPLC-QTOF MS)来评估血清和血浆样本中CLD发展为肝癌过程中的代谢变化。将使用从新诊断的肝细胞癌患者和匹配的肝硬变对照中收集的血清和血浆样本。确定的代谢生物标记物将通过将它们的串联质谱学数据与商业上可获得的标准化合物产生的数据进行比较来验证。(2)研究CLD向肝细胞癌发展过程中可能发生改变的关键代谢和信号通路。具体地说，我们将利用以途径为中心的方法，整合来自多项研究的实验结果，包括我们之前的蛋白质组学和糖组学研究，以提供肝细胞癌变化的“分子图谱”，以帮助设计诊断和治疗开发的靶点。我们期待这项研究的结果，以加强我们对疾病进展和候选肝细胞癌生物标志物在代谢和信号通路中的功能参与的理解。 公共卫生相关性：确定临床上适用的生物标志物，在高危人群中发现肝硬变患者的早期肝细胞癌(HCC)，对疾病管理和患者健康具有潜在的深远影响。这个项目很重要，因为大多数肝细胞癌患者是在晚期确诊的，治疗选择有限。迫切需要确定可用于肝细胞癌早期检测的生物标志物。该项目将利用这项研究和其他研究中确定的标记来研究可能与肝细胞癌进展相关的指纹。除了筛选高危人群的疾病早期迹象外，已识别的生物标志物及其在代谢和信号通路中的功能参与知识可用于设计和测试改进的治疗策略。