Dengler, Mirko and Staufer, Katharina and Huber, Heidemarie and Stauber, Rudolf and Bantel, Heike and Weiss, Karl Heinz and Starlinger, Patrick and Pock, Hannelore and Kloeters-Plachky, Petra and Gotthardt, Daniel N. and Rauch, Peter and Lackner, Carolin and Stift, Judith and Brostjan, Christine and Gruenberger, Thomas and Kumada, Takashi and Toyoda, Hidenori and Tada, Toshifumi and Weiss, Thomas S. and Trauner, Michael and Mikulits, Wolfgang (2017) Soluble Axl is an accurate biomarker of cirrhosis and hepatocellular carcinoma development: results from a large scale multicenter analysis. ONCOTARGET, 8 (28). pp. 46234-46248. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
Patients with chronic liver disease (CLD) and cirrhosis are at high risk for hepatocellular carcinoma (HCC). Current diagnostic tools for HCC detection include imaging techniques and serum biomarkers such as a-fetoprotein (AFP). Yet, these methods are limited in sensitivity and specificity to accurately detect early HCC. Here we focused on the potential of soluble Axl (sAxl) as a biomarker in CLD patients by analyzing serum samples of 1067 patients and healthy controls from centers in Europe and Asia. We show that serum concentrations of sAxl were significantly increased at early (82.57 ng/mL) and later stages of HCC (114.50 ng/mL) as compared to healthy controls (40.15 ng/mL). Notably, no elevated sAxl levels were detected in patients with CLD including chronic viral hepatitis, autoimmune hepatitis, cholestatic liver disease, or non-alcoholic fatty liver disease versus healthy controls. Furthermore, sAxl did not rise in liver adenomas or cholangiocarcinoma (CCA). Yet, patients with advanced fibrosis (F3) or cirrhosis (F4) showed enhanced sAxl concentrations (F3: 54.67 ng/mL; F4: 94.74 ng/mL). Hepatic myofibroblasts exhibited an increased release of sAxl, suggesting that elevated sAxl levels arise from these cells during fibrosis. Receiver operating characteristic curve analysis of sAxl displayed a strongly increased sensitivity and specificity to detect both cirrhosis (80.8%/92.0%) and HCC (83.3%/86.7%) with an area under the curve of 0.935/0.903 as compared to AFP. In conclusion, sAxl shows high diagnostic accuracy at early stage HCC as well as cirrhosis, thereby outperforming AFP. Importantly, sAxl remains normal in most common CLDs, liver adenomas and CCA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS; DES-GAMMA-CARBOXYPROTHROMBIN; CHRONIC LIVER-DISEASE; KINASE RECEPTOR AXL; ALPHA-FETOPROTEIN; PLASMA-CONCENTRATIONS; TYROSINE KINASE; UNITED-STATES; PROTEIN; GAS6; soluble Axl; biomarker; fibrosis; cirrhosis; hepatocellular carcinoma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 28 Feb 2019 07:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1546 |
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