title: 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: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Thilo
authors: T
authors: Bracht
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Vincent
authors: V
authors: Schweinsberg
authors: ‡Department of Gastroenterology and Hepatology, University Hospital of Essen, 45122 Essen, Germany.
authors: Martin
authors: M
authors: Trippler
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Michael
authors: M
authors: Kohl
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Maike
authors: M
authors: Ahrens
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Juliet
authors: J
authors: Padden
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Wael
authors: W
authors: Naboulsi
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Katalin
authors: K
authors: Barkovits
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Dominik A
authors: DA
authors: Megger
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Martin
authors: M
authors: Eisenacher
authors: §Genome British Columbia Proteomics Center, University of Victoria, Victoria, BC V8P 5C2, Canada.
authors: Christoph H
authors: CH
authors: Borchers
authors: ‡Department of Gastroenterology and Hepatology, University Hospital of Essen, 45122 Essen, Germany.
authors: Jörg F
authors: JF
authors: Schlaak
authors: ⊥Department of Medicine (Cancer Research), Molecular Oncology Risk-Profile Evaluation, University Hospital of Essen, 45122 Essen, Germany.
authors: Andreas-Claudius
authors: AC
authors: Hoffmann
authors: ¶Department of General, Visceral, and Transplantation Surgery, University Hospital of Essen, 45122 Essen, Germany.
authors: Frank
authors: F
authors: Weber
authors: □ Department of Pathology, University Hospital of Essen, 45147 Essen, Germany.
authors: Hideo A
authors: HA
authors: Baba
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.|#Leibniz Institute for Analytical Sciences-ISAS, 44139 Dortmund, Germany.
authors: Helmut E
authors: HE
authors: Meyer
authors: †Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Barbara
authors: B
authors: Sitek
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D000071234:Lumican; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C054447:COL14A1 protein, human; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D006023:Glycoproteins; C000604306:LUM protein, human; D000071234:Lumican; C400752:MFAP4 protein, human; D003094:Collagen; D007632:Keratan Sulfate
keywords: MFAP4; cirrhosis; fibrosis; fibulin-5; hepatic fibrosis; label-free proteomics; liver; lumican; multiple reaction monitoring; selected reaction monitoring