title: Detection of novel biomarkers of liver cirrhosis by proteomic analysis.
abstract: Hepatic cirrhosis is a life-threatening disease arising from different chronic liver disorders. One major cause for hepatic cirrhosis is chronic hepatitis C. Chronic hepatitis C is characterized by a highly variable clinical course, with at least 20% developing liver cirrhosis within 40 years. Only liver biopsy allows a reliable evaluation of the course of hepatitis C by grading inflammation and staging fibrosis, and thus serum biomarkers for hepatic fibrosis with high sensitivity and specificity are needed. To identify new candidate biomarkers for hepatic fibrosis, we performed a proteomic approach of microdissected cirrhotic septa and liver parenchyma cells. In cirrhotic septa, we detected an increasing expression of cell structure associated proteins, including actin, prolyl 4-hydroxylase, tropomyosin, calponin, transgelin, and human microfibril-associated protein 4 (MFAP-4). Tropomyosin, calponin, and transgelin reflect a contribution of activated stellate cells/myofibroblasts to chronic liver injury. The expression of tropomyosin, transgelin, and MFAP-4, an extracellular matrix associated protein, were further evaluated by immunohistochemistry. Tropomyosin and MFAP-4 demonstrated high serum levels in patients with hepatic cirrhosis of different causes.
  
  
  CONCLUSIONS
  A quantitative analysis of MFAP-4 serum levels in a large number of patients showed MFAP-4 as novel candidate biomarker with high diagnostic accuracy for prediction of nondiseased liver versus cirrhosis [area under receiver operating characteristic curve (AUC) = 0.97, P < 0.0001] as well as stage 0 versus stage 4 fibrosis (AUC = 0.84, P < 0.0001), and stages 0 to 3 versus stage 4 fibrosis (AUC = 0.76, P < 0.0001).
authors.affiliation: Department of Internal Medicine, Bergmannsheil, Ruhr-Universität Bochum, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mölleken
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.forename: Corinna
authors.initials: C
authors.lastname: Henkel
authors.forename: Gereon
authors.initials: G
authors.lastname: Poschmann
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wiese
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.forename: Christoph
authors.initials: C
authors.lastname: Broelsch
authors.forename: Markus
authors.initials: M
authors.lastname: Reiser
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.forename: Ida
authors.initials: I
authors.lastname: Tornøe
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D040901:Proteomics; D012372:ROC Curve; D014335:Tropomyosin / Q000097:blood
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C400752:MFAP4 protein, human; D014335:Tropomyosin