title: Phospho-Network Analysis Identifies and Quantifies Hepatitis C Virus (HCV)-induced Hepatocellular Carcinoma (HCC) Proteins Regulating Viral-mediated Tumor Growth.
abstract: BACKGROUND
  Patients with chronic hepatitis C virus (HCV) infection are at risk of serious complications of cirrhosis and hepatocellular carcinoma (HCC). Mass spectrometry (MS) is a versatile methodology that produces a global proteomic landscape for analysis of cancer mechanisms.
  
  
  METHODS
  Using multiplex peptide stable isotopic labeling and immobilized metal affinity chromatography (IMAC), we enriched and quantified the phosphoproteome of HCC, with and without HCV. While raw data identified protein targets based on expression alone, we also used abundance groups for comprehensive functional analysis.
  
  
  RESULTS
  Analysis of functional differences highlighted deregulated phosphoprotein networks. This uncovered additional candidates that could be directly derived from the MS data. Cellular processes and pathways that may differ with HCV infection include: cytoskeletal dynamics, insulin response, gene expression, and PI3K/AKT oncogenesis.
  
  
  CONCLUSIONS
  This function-focused workflow provides a simple framework to analyze MS data. Phosphoproteome quantitation with inclusive functional analysis can generate hypotheses for liver cancer research to improve early screening and identification of molecular targets for therapy.
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A Department of Hematology and Oncology, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Nu T
authors: NT
authors: Lu
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Natalie M
authors: NM
authors: Liu
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: James Q
authors: JQ
authors: Vu
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Darshil
authors: D
authors: Patel
authors: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Whitaker
authors: W
authors: Cohn
authors: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, U.S.A Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles CA, U.S.A.
authors: Joe
authors: J
authors: Capri
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Mary
authors: M
authors: Ziegler
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Nikita
authors: N
authors: Patel
authors: Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, U.S.A.
authors: Angela
authors: A
authors: Tramontano
authors: The Foundation for Liver Research-The Institute for Hepatology, London, U.K.
authors: Roger
authors: R
authors: Williams
authors: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, U.S.A.
authors: Julian
authors: J
authors: Whitelegge
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, U.S.A sfrench@mednet.ucla.edu.
authors: Samuel W
authors: SW
authors: French
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D010455:Peptides; D010750:Phosphoproteins; D020543:Proteome
keywords: Hepatocellular carcinoma; hepatitis C virus; mass spectrometry; phosphoproteomics