caa a22 4500 445798068 CHVBK 20180317145132.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s10620-011-1745-4 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1745-4 Novel Biomarker Candidates to Predict Hepatic Fibrosis in HepatitisC Identified by Serum Proteomics [Elektronische Daten] [Libang Yang, Kyle Rudser, LeeAnn Higgins, Hugo Rosen, Atif Zaman, Christopher Corless, Larry David, Glenn Gourley] 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 hepatitisC 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: complementC4-A and inter-alpha-trypsin inhibitor heavy chainH4. Springer Science+Business Media, LLC, 2011 Hepatic fibrosis nationallicence HepatitisC nationallicence iTRAQ nationallicence DIGE nationallicence Gel electrophoresis nationallicence Mass spectroscopy nationallicence iTRAQ : Isobaric tags for relative and absolute quantitation nationallicence DIGE : Difference in gel electrophoresis nationallicence HCV : HepatitisC virus nationallicence Yang Libang Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 185, 55455, Minneapolis, MN, USA aut Rudser Kyle Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA aut Higgins LeeAnn Departments of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA aut Rosen Hugo Department of Medicine, University of Colorado, Denver, CO, USA aut Zaman Atif Department of Medicine, OHSU, Portland, OR, USA aut Corless Christopher Department of Pathology, OHSU, Portland, OR, USA aut David Larry Department of Biochemistry and Molecular Biology, OHSU, Portland, OR, USA aut Gourley Glenn Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 185, 55455, Minneapolis, MN, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/11(2011-11-01), 3305-3315 0163-2116 56:11<3305 2011 56 10620 https://doi.org/10.1007/s10620-011-1745-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1745-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Libang Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 185, 55455, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Rudser Kyle Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Higgins LeeAnn Departments of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Rosen Hugo Department of Medicine, University of Colorado, Denver, CO, USA aut NATIONALLICENCE 700 1- Zaman Atif Department of Medicine, OHSU, Portland, OR, USA aut NATIONALLICENCE 700 1- Corless Christopher Department of Pathology, OHSU, Portland, OR, USA aut NATIONALLICENCE 700 1- David Larry Department of Biochemistry and Molecular Biology, OHSU, Portland, OR, USA aut NATIONALLICENCE 700 1- Gourley Glenn Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 185, 55455, Minneapolis, MN, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/11(2011-11-01), 3305-3315 0163-2116 56:11<3305 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer