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- Title:
Detection of novel biomarkers of liver cirrhosis by proteomic analysis.
- Document type:
- Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
- Author(s):
- Mölleken, C; Sitek, B; Henkel, C; Poschmann, G; Sipos, B; Wiese, S; Warscheid, B; Broelsch, C; Reiser, M; Friedman, SL; Tornøe, I; Schlösser, A; Klöppel, G; Schmiegel, W; Meyer, HE; Holmskov, U; Stühler, K
- 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. CONCLUSION: 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).
- Journal title abbreviation:
- Hepatology
- Year:
- 2009
- Journal volume:
- 49
- Journal issue:
- 4
- Pages contribution:
- 1257-66
- Language:
- eng
- Fulltext / DOI:
- doi:10.1002/hep.22764
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/19177598
- Print-ISSN:
- 0270-9139
- TUM Institution:
- Institut für Allgemeine Pathologie und Pathologische Anatomie
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