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Novel Biomarker Candidates to Predict Hepatic Fibrosis in Hepatitis C Identified by Serum Proteomics

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Abstract

Background

Liver biopsy remains the gold standard to assess hepatic fibrosis. It is desirable to predict hepatic fibrosis without the need for invasive liver biopsy. Proteomic techniques allow unbiased assessment of proteins and might be useful to identify proteins related to hepatic fibrosis.

Aims

We utilized two different proteomic methods to identify serum proteins as candidate biomarkers to predict hepatic fibrosis stage in patients with chronic hepatitis C virus (HCV) infection.

Methods

Serum was obtained from 24 people with chronic HCV at time of liver biopsy and from 6 normals. Liver biopsy fibrosis was staged 1–4 (Batts–Ludwig). Pooled serum samples (six in each of four fibrosis groups and controls) were analyzed with 4- and 8-plex isobaric tags for relative and absolute quantitation (iTRAQ), determining protein identification (ID) and ratios of relative protein abundance. Nonpooled samples were analyzed with two-dimensional (2-D) gels and difference in gel electrophoresis (DIGE) comparing different samples on the same gel and across gels. Spots varying among groups were measured with densitometry, excised, digested, and submitted for tandem mass spectrometry (MS/MS) protein ID.

Results

iTRAQ identified 305 proteins (minimum 99% ID confidence); 66 were increased or decreased compared with controls. Some proteins were increased or decreased for specific fibrosis scores. From 704 DIGE protein spots, 66 were chosen, 41 excised, and 135 proteins identified, since one gel spot often identified more than one protein.

Conclusions

Both proteomic methods identified two proteins as biomarker candidates for predicting hepatic fibrosis: complement C4-A and inter-alpha-trypsin inhibitor heavy chain H4.

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Abbreviations

iTRAQ:

Isobaric tags for relative and absolute quantitation

DIGE:

Difference in gel electrophoresis

HCV:

Hepatitis C virus

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Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 185, Minneapolis, MN, 55455, USA

    Libang Yang & Glenn R. Gourley

  2. Departments of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA

    LeeAnn Higgins

  3. Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA

    Kyle D. Rudser

  4. Department of Medicine, University of Colorado, Denver, CO, USA

    Hugo R. Rosen

  5. Department of Medicine, OHSU, Portland, OR, USA

    Atif Zaman

  6. Department of Pathology, OHSU, Portland, OR, USA

    Christopher L. Corless

  7. Department of Biochemistry and Molecular Biology, OHSU, Portland, OR, USA

    Larry David

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  1. Libang Yang
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Correspondence to Glenn R. Gourley.

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Yang, L., Rudser, K.D., Higgins, L. et al. Novel Biomarker Candidates to Predict Hepatic Fibrosis in Hepatitis C Identified by Serum Proteomics. Dig Dis Sci 56, 3305–3315 (2011). https://doi.org/10.1007/s10620-011-1745-4

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  • DOI: https://doi.org/10.1007/s10620-011-1745-4

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