Notch activity characterizes a common hepatocellular carcinoma subtype with unique molecular and clinicopathologic features.

ABSTRACT:

Background & aims

The hepatocyte Notch pathway is a pathogenic factor in non-alcoholic steatohepatitis (NASH)-associated fibrosis, but its role in hepatocellular carcinoma (HCC) is less well defined. Herein, we aimed to characterize the molecular and clinical features of Notch-active human HCC, and to investigate the mechanisms by which Notch affects NASH-driven HCC.

Methods

Using a 14-gene Notch score, we stratified human HCCs from multiple comprehensively profiled datasets. We performed gene set enrichment analyses to compare Notch-active HCCs with published HCC subtype signatures. Next, we sorted Notch-active hepatocytes from Notch reporter mice for RNA sequencing and characterized Notch-active tumors in an HCC model combining a carcinogen and a NASH-inducing diet. We use

SUBMITTER: Zhu C 

PROVIDER: S-EPMC7897246 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature