title: Metabolomic Characterization of Hepatocellular Carcinoma in Patients with Liver Cirrhosis for Biomarker Discovery.
abstract: Background:Metabolomics plays an important role in providing insight into the etiology and mechanisms of hepatocellular carcinoma (HCC). This is accomplished by a comprehensive analysis of patterns involved in metabolic alterations in human specimens. This study compares the levels of plasma metabolites in HCC cases versus cirrhotic patients and evaluates the ability of candidate metabolites in distinguishing the two groups. Also, it investigates the combined use of metabolites and clinical covariates for detection of HCC in patients with liver cirrhosis.Methods:Untargeted analysis of metabolites in plasma from 128 subjects (63 HCC cases and 65 cirrhotic controls) was conducted using gas chromatography coupled to mass spectrometry (GC-MS). This was followed by targeted evaluation of selected metabolites. LASSO regression was used to select a set of metabolites and clinical covariates that are associated with HCC. The performance of candidate biomarkers in distinguishing HCC from cirrhosis was evaluated through a leave-one-out cross-validation based on area under the receiver operating characteristics (ROC) curve.Results:We identified 11 metabolites and three clinical covariates that differentiated HCC cases from cirrhotic controls. Combining these features in a panel for disease classification using support vector machines (SVM) yielded better area under the ROC curve compared with alpha-fetoprotein (AFP).Conclusions:This study demonstrates the combination of metabolites and clinical covariates as an effective approach for early detection of HCC in patients with liver cirrhosis.Impact:Further investigation of these findings may improve understanding of HCC pathophysiology and possible implication of the metabolites in HCC prevention and diagnosis.Cancer Epidemiol Biomarkers Prev; 26(5); 675-83. ©2016 AACR.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Cristina
authors.initials: C
authors.lastname: Di Poto
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ferrarini
authors.affiliation: Department of Biostatistics, School of Public Health, Brown University, Providence, Rhode Island.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Rency S
authors.initials: RS
authors.lastname: Varghese
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Chao
authors.initials: C
authors.lastname: Tu
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Minkun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Nezami Ranjbar
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Yue
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC.
authors.forename: Chirag S
authors.initials: CS
authors.lastname: Desai
authors.affiliation: Division of Gastroenterology & Hepatology, Johns Hopkins University, Sibley Memorial Hospital, Washington, DC.
authors.forename: Kirti
authors.initials: K
authors.lastname: Shetty
authors.affiliation: Department of Mathematics and Statistics, Georgetown University, Washington DC.
authors.forename: Mahlet G
authors.initials: MG
authors.lastname: Tadesse
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC. hwr@georgetown.edu.
authors.forename: Habtom W
authors.initials: HW
authors.lastname: Ressom
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor