Analysis of disease-associated protein expression using quantitative proteomics—fibulin-5 is expressed in association with hepatic fibrosis.

Abstract

Hepatic fibrosis and cirrhosis are major health problems worldwide. Until now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. To develop noninvasive diagnostic assays for the assessment of liver fibrosis, it is urgently necessary to identify molecules that are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n = 77). Finally, we performed a targeted proteomics approach, multiple reaction monitoring (MRM), to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM), and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.

• Authors: Thilo Bracht, Vincent Schweinsberg, Martin Trippler, Michael Kohl, Maike Ahrens, Juliet Padden, Wael Naboulsi, Katalin Barkovits, Dominik A Megger, Martin Eisenacher, Christoph H Borchers, Jörg F Schlaak, Andreas-Claudius Hoffmann, Frank Weber, Hideo A Baba, Helmut E Meyer, Barbara Sitek
• Journal: Journal of proteome research (J Proteome Res) Vol. 14 Issue 5 Pg. 2278-86 (May 01 2015) ISSN: 1535-3907 [Electronic] United States
• PMID: 25807371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• COL14A1 protein, human
• Carrier Proteins
• Chondroitin Sulfate Proteoglycans
• Extracellular Matrix Proteins
• FBLN5 protein, human
• Glycoproteins
• LUM protein, human
• Lumican
• MFAP4 protein, human
• Collagen
• Keratan Sulfate

Topics

• Biomarkers (metabolism)
• Biopsy
• Carrier Proteins (genetics, metabolism)
• Chondroitin Sulfate Proteoglycans (genetics, metabolism)
• Cohort Studies
• Collagen (genetics, metabolism)
• Extracellular Matrix Proteins (genetics, metabolism)
• Female
• Glycoproteins (genetics, metabolism)
• Hepatitis B (complications, diagnosis, genetics, virology)
• Hepatitis C (complications, diagnosis, genetics, virology)
• Humans
• Keratan Sulfate (genetics, metabolism)
• Liver (metabolism, pathology, virology)
• Liver Cirrhosis (complications, diagnosis, genetics, virology)
• Lumican
• Male
• Middle Aged
• Proteomics (methods)
• Transcriptome