SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma

Authors

  • E. Ellen Schwegler,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA
    2. Center for Biomedical Proteomics, Eastern Virginia Medical School, Norfolk, VA
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  • Lisa Cazares,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA
    2. Center for Biomedical Proteomics, Eastern Virginia Medical School, Norfolk, VA
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  • Laura F. Steel,

    1. Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, PA
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  • Bao-Ling Adam,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA
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    • B.-L.A. is currently affiliated with Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA.

  • David A. Johnson,

    1. Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA
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  • O. John Semmes,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA
    2. Center for Biomedical Proteomics, Eastern Virginia Medical School, Norfolk, VA
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  • Timothy M. Block,

    1. Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, PA
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  • Jorge A. Marrero,

    1. Division of Gastrotenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
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  • Richard R. Drake

    Corresponding author
    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA
    2. Center for Biomedical Proteomics, Eastern Virginia Medical School, Norfolk, VA
    • Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 W. Olney, Norfolk, VA 23507
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    • fax: 757-624-2255


  • Conflict of interest: Nothing to report.

Abstract

Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC). A cohort of 170 serum samples obtained from subjects in the United States with no liver disease (n = 39), liver diseases not associated with cirrhosis (n = 36), cirrhosis (n = 38), or HCC (n = 57) were applied to metal affinity protein chips for protein profiling by SELDI-TOF MS. Across the four test groups, 38 differentially expressed proteins were used to generate multiple decision classification trees to distinguish the known disease states. Analysis of a subset of samples with only hepatitis C virus (HCV)-related disease was emphasized. The serum protein profiles of control patients were readily distinguished from each HCV-associated disease state. Two-way comparisons of chronic hepatitis C, HCV cirrhosis, or HCV-HCC versus healthy had a sensitivity/specificity range of 74% to 95%. For distinguishing chronic HCV from HCV-HCC, a sensitivity of 61% and a specificity of 76% were obtained. However, when the values of known serum markers α fetoprotein, des-gamma carboxyprothrombin, and GP73 were combined with the SELDI peak values, the sensitivity and specifity improved to 75% and 92%, respectively. In conclusion, SELDI-TOF MS serum profiling is able to distinguish HCC from liver disease before cirrhosis as well as cirrhosis, especially in patients with HCV infection compared with other etiologies. (HEPATOLOGY 2005;41:634–642.)

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