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J Proteome Res. 2015 May 1;14(5):2278-86. doi: 10.1021/acs.jproteome.5b00053. Epub 2015 Apr 6.

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

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†Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
‡Department of Gastroenterology and Hepatology, University Hospital of Essen, 45122 Essen, Germany.
§Genome British Columbia Proteomics Center, University of Victoria, Victoria, BC V8P 5C2, Canada.
⊥Department of Medicine (Cancer Research), Molecular Oncology Risk-Profile Evaluation, University Hospital of Essen, 45122 Essen, Germany.
¶Department of General, Visceral, and Transplantation Surgery, University Hospital of Essen, 45122 Essen, Germany.
□ Department of Pathology, University Hospital of Essen, 45147 Essen, Germany.
#Leibniz Institute for Analytical Sciences-ISAS, 44139 Dortmund, Germany.


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.


MFAP4; cirrhosis; fibrosis; fibulin-5; hepatic fibrosis; label-free proteomics; liver; lumican; multiple reaction monitoring; selected reaction monitoring

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