title: LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma.
abstract: Associating changes in protein levels with the onset of cancer has been widely investigated to identify clinically relevant diagnostic biomarkers. In the present study, we analyzed sera from 205 patients recruited in the United States and Egypt for biomarker discovery using label-free proteomic analysis by LC-MS/MS. We performed untargeted proteomic analysis of sera to identify candidate proteins with statistically significant differences between hepatocellular carcinoma (HCC) and patients with liver cirrhosis. We further evaluated the significance of 101 proteins in sera from the same 205 patients through targeted quantitation by MRM on a triple quadrupole mass spectrometer. This led to the identification of 21 candidate protein biomarkers that were significantly altered in both the United States and Egyptian cohorts. Among the 21 candidates, ten were previously reported as HCC-associated proteins (eight exhibiting consistent trends with our observation), whereas 11 are new candidates discovered by this study. Pathway analysis based on the significant proteins reveals upregulation of the complement and coagulation cascades pathway and downregulation of the antigen processing and presentation pathway in HCC cases versus patients with liver cirrhosis. The results of this study demonstrate the power of combining untargeted and targeted quantitation methods for a comprehensive serum proteomic analysis, to evaluate changes in protein levels and discover novel diagnostic biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD001171 (http://proteomecentral.proteomexchange.org/dataset/PXD001171).
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Tsung-Heng
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Ehwang
authors.initials: E
authors.lastname: Song
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
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, USA.
authors.forename: Minkun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Rency S
authors.initials: RS
authors.lastname: Varghese
authors.affiliation: Department of Mathematics and Statistics, Georgetown University, Washington, DC, USA.
authors.forename: Mahlet G
authors.initials: MG
authors.lastname: Tadesse
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, Tanta University, Tanta, Egypt.
authors.forename: Dina Hazem
authors.initials: DH
authors.lastname: Ziada
authors.affiliation: MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Chirag S
authors.initials: CS
authors.lastname: Desai
authors.affiliation: Johns Hopkins University, Gastroenterology & Hepatology at Sibley, Washington, DC, USA.
authors.forename: Kirti
authors.initials: K
authors.lastname: Shetty
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Mechref
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Habtom W
authors.initials: HW
authors.lastname: Ressom
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
keywords: Biomedicine; Cancer biomarker discovery; Hepatocellular carcinoma; LC-MS/MS; Liver cirrhosis; MRM