High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.
Transl Oncol
; 12(2): 256-268, 2019 Feb.
Article
de En
| MEDLINE
| ID: mdl-30439626
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Type d'étude:
Prognostic_studies
/
Risk_factors_studies
Langue:
En
Journal:
Transl Oncol
Année:
2019
Type de document:
Article
Pays d'affiliation:
Autriche