%0 Journal Article
%T High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
%A Alexandra K. Kiemer
%A Alexandra Lipfert
%A Andrea Th¨¹ringer
%A Anita Kuldeep Mehta
%A Clemens Diwoky
%A Cornelia Stumptner
%A Heimo M¨¹ller
%A Johannes Haybaeck
%A Julia Unterluggauer
%A K.P.R. Nilsson
%A Kensuke Kojima
%A Kira Bettermann
%A Leopold F. Fr£¿hlich
%A Michael G. Schimek
%A Nabeel M. Bardeesy
%A Nicole Golob-Schwarzl
%A Pavel Strnad
%A Richard Moriggl
%A Sonja M. Kessler
%A Stefanie Krassnig
%A Tatjana Stojakovic
%A Thomas Kolbe
%A Thomas M. Magin
%A Thomas R¨¹licke
%A Vendula Svendova
%A Vineet Mahajan
%A Xintong Chen
%A Yujin Hoshida
%J Archive of "Translational Oncology".
%D 2019
%R 10.1016/j.tranon.2018.10.010
%X 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
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234703/