Summary of Study ST000865

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000602. The data can be accessed directly via it's Project DOI: 10.21228/M8VH5Q This work is supported by NIH grant, U2C- DK119886.

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Study IDST000865
Study TitleIdentification of Race-Associated Metabolite Biomarkers for Hepatocellular Carcinoma
Study SummaryIntroduction: Metabolomics provides simultaneous assessment of a broad range of metabolites that can potentially serve as indicators of the overall physiology status as well as the response to host and environmental stimuli. It has been broadly used for biomarker discovery and characterization of complex diseases such as cancer. The evaluation of the changes in the levels of metabolites in samples stratified by race could lead to the identification of more reliable biomarkers than those obtained through whole-population-based approaches. In this study, we used plasma samples collected from patients recruited at MedStar Georgetown University Hospital to investigate metabolites that may be associated with hepatocellular carcinoma (HCC) in a race-specific manner. Methods: Plasma samples were protein depleted using a solution composed of acetonitrile:isopropanol:water (3:3:2) containing a mixture of isotope-labeled internal standards. The extracted metabolites were trimethylsilyl derivatized prior to analysis by GC-MS. A quality control (QC) sample derived by pooling plasma from multiple subjects was run in between samples to assess reproducibility. A mixture of fatty acids methyl esters (FAMEs) and alkane standards was run for retention index calibration. The mixture of isotope-labeled internal standards was used to evaluate the reproducibility of the GC-MS data across multiple runs. Preliminary Data: Plasma samples collected from 40 HCC cases and 44 patients with liver cirrhosis were analyzed. The cirrhotic controls were frequency matched with the HCC cases by demographic variables. The participants included 19 African Americans (AA) and 50 European Americans (EA). The analysis targeted 46 metabolites for quantitative analysis by Agilent GC-qMS in selected ion monitoring (SIM) mode. The data were pre-processed by the Automated Mass Spectral Deconvolution and Identification System (AMDIS) for peak detection, deconvolution, and identification. The resulting peaks were aligned using Mass Profiler Professional (MPP) from Agilent Technologies. A LASSO regression model was applied to select metabolites with significant changes in HCC vs. cirrhosis in three groups: (1) AA and EA combined; (2) AA only; and (3) EA only. Also, metabolites that distinguish HCC cases from cirrhosis in the three groups were selected by considering only those subjects with Hepatitis C virus (HCV) infection. The performances of the metabolites selected by LASSO in each group were evaluated through a leave-one-out cross-validation. We identified race-specific metabolites that differentiated HCC cases from cirrhotic controls, yielding better area under the ROC curve compared to alpha-fetoprotein (AFP) - the serological marker widely used for the diagnosis of HCC. Novel Aspect: We identified race-associated metabolites that are significantly altered in HCC vs. cirrhosis, suggesting the potential role of race in HCC.
Institute
Georgetown University
DepartmentOncology
LaboratoryRessom Lab (PI: Habtom W. Ressom, email address hwr@georgetown.edu)
Last NameRessom
First NameHabtom
Address4000 Reservoir Rd. NW, Room 175, Washington, DC 20007
Emailhwr@georgetown.edu
Phone2026872283
Submit Date2017-08-14
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailGC-MS
Release Date2018-03-02
Release Version1
Habtom Ressom Habtom Ressom
https://dx.doi.org/10.21228/M8VH5Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Collection:

Collection ID:CO000886
Collection Summary:Blood collection Adult patients were recruited from the hepatology clinic at MedStar Georgetown University Hospital (MGUH).All participants provided informed consent to the study approved by the Institutional Review Board (IRB) at Georgetown University. The patients were diagnosed to have liver cirrhosis on the basis of established clinical, laboratory and/or imaging criteria. Cases were diagnosed to have HCC based on well-established diagnostic imaging criteria and/or histology. Clinical stages for HCC cases were determined based on the tumor-node-metastasis (TNM) staging system. Controls were required to be HCC free for at least 6 months from the time of study entry. Race information was collected from patients’ self-report. Through peripheral venipuncture, single blood sample was drawn into 10 mL BD Vacutainer sterile vacuum tube in the presence of EDTA anticoagulant.
Collection Protocol ID:1_Collection
Sample Type:Blood
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