High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.

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-a

SUBMITTER: Golob-Schwarzl N 

PROVIDER: S-EPMC6234703 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature