Please use this identifier to cite or link to this item: doi:10.22028/D291-28047
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Title: High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
Author(s): Golob-Schwarzl, Nicole
Bettermann, Kira
Mehta, Anita Kuldeep
Kessler, Sonja M.
Unterluggauer, Julia
Krassnig, Stefanie
Kojima, Kensuke
Chen, Xintong
Hoshida, Yujin
Bardeesy, Nabeel M.
Müller, Heimo
Svendova, Vendula
Schimek, Michael G.
Diwoky, Clemens
Lipfert, Alexandra
Mahajan, Vineet
Stumptner, Cornelia
Thüringer, Andrea
Fröhlich, Leopold F.
Stojakovic, Tatjana
Nilsson, K.P.R.
Kolbe, Thomas
Rülicke, Thomas
Magin, Thomas M.
Strnad, Pavel
Kiemer, Alexandra
Moriggl, Richard
Haybaeck, Johannes
Language: English
Title: Translational Oncology
Volume: 12
Issue: 2
Startpage: 256
Endpage: 268
Publisher/Platform: Elsevier
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
ISSN: 1936-5233
Date of registration: 11-Jul-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Alexandra K. Kiemer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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