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: 8100460
• 负责人: Habtom W Ressom
• 金额: $ 16.19万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100460
• 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; Metabolic Pathway; 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）：多水平组学数据的积累为更好地了解慢性肝病（CLD）进展为肝细胞癌（HCC）提供了机会。已经检测到多种HCC相关的分子改变。然而，由于缺乏良好的诊断标志物和治疗策略，以及由于疾病在人群中的异质性，对HCC发展机制的一致理解仍然有限。HCC中复杂的多基因分子通路的评估仍然是一个困难的挑战。该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&lt;dat治疗HCC。</keyword></keywords>具体而言，本项目通过超高效液相色谱-四极杆飞行时间质谱（UPLC-QTOF MS）评价血清和血浆样本中CLD向HCC进展过程中的代谢变化。将使用从新诊断的HCC病例和匹配的HCC对照中采集的血清和血浆样本。将通过将其串联质谱数据与市售标准化合物生成的数据进行比较，验证已鉴别的代谢生物标志物。(2)研究在CLD向HCC进展过程中可能发生改变的关键代谢和信号通路。具体来说，我们将利用一种以路径为中心的方法，通过整合多项研究的实验结果，包括我们以前的蛋白质组学和糖组学研究，提供HCC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，以提高我们对疾病进展和候选HCC生物标志物在代谢和信号通路中的功能参与的理解。 公共卫生关系：定义临床上适用的生物标志物，检测早期肝细胞癌（HCC）的高风险人群中的肝细胞癌患者有潜在的疾病管理和患者健康的深远影响。这个项目很重要，因为大多数HCC患者都是在晚期被诊断出来的，治疗选择有限。迫切需要鉴定可用于早期检测HCC的生物标志物。该项目将利用本研究和其他研究中确定的标志物来研究可能与HCC进展相关的指纹。除了筛查高风险人群的疾病早期体征外，所确定的生物标志物及其在代谢和信号传导途径中的功能参与的知识可用于设计和测试改进的治疗策略。

项目成果

LC-MS-based metabolomics.

• DOI: 10.1039/c1mb05350g
• 发表时间: 2012-02
• 期刊: Molecular bioSystems
• 作者: Zhou B;Xiao JF;Tuli L;Ressom HW
• 通讯作者: Ressom HW

Metabolite identification and quantitation in LC-MS/MS-based metabolomics.

• DOI: 10.1016/j.trac.2011.08.009
• 发表时间: 2012-02-01
• 期刊: TRAC-TRENDS IN ANALYTICAL CHEMISTRY
• 影响因子: 13.1
• 作者: Xiao, Jun Feng;Zhou, Bin;Ressom, Habtom W.
• 通讯作者: Ressom, Habtom W.

Prioritization of putative metabolite identifications in LC-MS/MS experiments using a computational pipeline.

• DOI: 10.1002/pmic.201200306
• 发表时间: 2013-01
• 期刊: PROTEOMICS
• 影响因子: 3.4
• 作者: Zhou, Bin;Xiao, Jun Feng;Ressom, Habtom W.
• 通讯作者: Ressom, Habtom W.

LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort.

• DOI: 10.1021/pr300673x
• 发表时间: 2012-12-07
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Xiao JF;Varghese RS;Zhou B;Nezami Ranjbar MR;Zhao Y;Tsai TH;Di Poto C;Wang J;Goerlitz D;Luo Y;Cheema AK;Sarhan N;Soliman H;Tadesse MG;Ziada DH;Ressom HW
• 通讯作者: Ressom HW

MetaboSearch: tool for mass-based metabolite identification using multiple databases.

• DOI: 10.1371/journal.pone.0040096
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Zhou B;Wang J;Ressom HW
• 通讯作者: Ressom HW