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PLoS One. 2018 Mar 14;13(3):e0192748. doi: 10.1371/journal.pone.0192748. eCollection 2018.

Identification of race-associated metabolite biomarkers for hepatocellular carcinoma in patients with liver cirrhosis and hepatitis C virus infection.

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Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America.
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, United States of America.
Department of Chemistry, Addis Ababa University, Addis Ababa, Ethiopia.
Department of Microbial, Cellular and Molecular Biology, Addis Ababa University, Addis Ababa, Ethiopia.
Department of Mathematics and Statistics, Georgetown University, Washington DC, United States of America.
Department of Biochemistry & Molecular Biology, College of Medicine, Howard University, Washington DC, United States of America.
Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina, United States of America.


Disparities in hepatocellular carcinoma (HCC) incidence and survival have been observed between ethnic groups including African-Americans (AA) and European-Americans (EA). The evaluation of the changes in the levels of metabolites in samples stratified by race could provide a snapshot of ethnically diverse disease related pathways and identify reliable biomarkers. In this study, we considered AA and EA to investigate metabolites that may be associated with HCC in a race-specific manner. The levels of 46 metabolites in plasma samples, collected from patients recruited at MedStar Georgetown University Hospital, were analyzed by Agilent GC-qMS in selected ion monitoring (SIM) mode. A least absolute shrinkage and selection operator (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 separately; and (3) EA separately. In addition, metabolites that distinguish HCC cases from cirrhosis in these three groups were selected by excluding those without 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 receiver operating characteristics (ROC) curve (AUC) compared to alpha-fetoprotein (AFP), the serological marker widely used for the diagnosis of HCC. This study sheds light on metabolites that could potentially be used as biomarkers for HCC by monitoring their levels in high-risk population of cirrhotic patients in a race-specific manner.

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