title: GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.
abstract: This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC) cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS). Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS) and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS). Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM) mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA) metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States of America.
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, United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States of America.
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, United States of America.
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, United States of America.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ferrarini
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Histology and Genetics, Tanta Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Naglaa I
authors.initials: NI
authors.lastname: Sarhan
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, Tanta Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Hanan
authors.initials: H
authors.lastname: Soliman
authors.affiliation: Department of Mathematics and Statistics, Georgetown University, Washington, DC, United States of America.
authors.forename: Mahlet G
authors.initials: MG
authors.lastname: Tadesse
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, Tanta Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Dina H
authors.initials: DH
authors.lastname: Ziada
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Roy
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Habtom W
authors.initials: HW
authors.lastname: Ressom
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000378:metabolism; D004534:Egypt; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor