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Title
High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
AuthorGolob-Schwarzl, Nicole ; Bettermann, Kira ; Kuldeep Mehta, Anita ; Kessler, Sonja M. ; Diwoky, Clemens
Published in
Translational Oncology, 2019, Vol. 12, Issue 2, page 256-268
Published2019
LanguageEnglish
Document typeJournal Article
URNurn:nbn:at:at-ubg:3-5075 Persistent Identifier (URN)
DOI10.1016/j.tranon.2018.10.010 
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 The work is publicly available
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High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype [3.25 mb]
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Abstract (English)

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.

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CC-BY-NC-ND-License (4.0)Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License