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Gewählte Publikation:

Golob-Schwarzi, N; Bettermann, K; Mehta, AK; Kessler, SM; Unterluggauer, J; Krassnig, S; Kojima, K; Chen, XT; Hoshida, Y; Bardeesy, NM; Muller, H; Svendova, V; Schimek, MG; Diwoky, C; Lipfert, A; Mahajan, V; Stumptner, C; Thuringer, A; Frohlich, LF; Stojakovic, T; Nilsson, KPR; Kolbe, T; Rulicke, T; Magin, TM; Strnad, P; Kiemer, AK; Moriggl, R; Haybaeck, J.
(2019): High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
TRANSL ONCOL. 2019; 12(2): 256-268. FullText FullText_BOKU

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 termedMallory-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: Weanalyzed 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.
Autor/innen der BOKU Wien:
Kolbe Thomas
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