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|Title:||High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype|
Mehta, Anita Kuldeep
Kessler, Sonja M.
Bardeesy, Nabeel M.
Schimek, Michael G.
Fröhlich, Leopold F.
Magin, Thomas M.
|Year of Publication:||2019|
|Publikation type:||Journal Article|
|Abstract:||BACKGROUND & AIMS: Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, and fibrosis at late stage. Disturbance of the keratin cytoskeleton and aggregation of keratins (KRTs) are essential for MDB formation. METHODS: We analyzed livers of aged Krt18−/− mice that spontaneously developed in the majority of cases SH-associated HCC independent of sex. Interestingly, the hepatic lipid profile in Krt18−/− mice, which accumulate KRT8, closely resembles human SH lipid profiles and shows that the excess of KRT8 over KRT18 determines the likelihood to develop SH-associated HCC linked with enhanced lipogenesis. RESULTS: Our analysis of the genetic profile of Krt18−/− mice with 26 human hepatoma cell lines and with data sets of >300 patients with HCC, where Krt18−/− gene signatures matched human HCC. Interestingly, a high KRT8/18 ratio is associated with an aggressive HCC phenotype. CONCLUSIONS: We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC.|
|DOI of the first publication:||10.1016/j.tranon.2018.10.010|
|Link to this record:||hdl:20.500.11880/27480|
|Date of registration:||11-Jul-2019|
|Faculty:||NT - Naturwissenschaftlich- Technische Fakultät|
|Department:||NT - Pharmazie|
|Professorship:||NT - Prof. Dr. Alexandra K. Kiemer|
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