A Mouse in vivo Model Mimicking MASH-Related HCC Pathogenesis.

Area of Science:

• Hepatology
• Oncology
• Translational Medicine

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASH) is increasingly linked to hepatocellular carcinoma (HCC).
• Existing preclinical models lack fidelity to human MASH-related HCC or have lengthy timelines.
• Accurate models are needed to understand MASH-driven HCC pathology and develop treatments.

Purpose of the Study:

• To develop a novel murine model for accelerated and accurate MASH-related HCC progression.
• To integrate chronic metabolic stress with oncogenic drivers for enhanced disease modeling.
• To establish a reliable platform for MASH-HCC research.

Main Methods:

• Mice were fed a choline-deficient, high-fat diet (CDAA-HFD).
• Hydrodynamic transfection introduced NRAS^G12V/AKT oncogenes.
• Disease progression and molecular profiles were analyzed via histopathology and transcriptomics.

Main Results:

• The combined CDAA-HFD and oncogene model rapidly progressed from steatohepatitis to HCC.
• Histopathology confirmed malignant lesions.
• Transcriptomic analysis revealed significant molecular overlap with human MASH-HCC, including lipid metabolism, ECM remodeling, and PI3K-Akt signaling pathway dysregulation.

Conclusions:

• The developed model accurately recapitulates key pathological and molecular features of human MASH-related HCC.
• This integrated dietary and genetic approach provides a high-fidelity preclinical platform.
• The model is valuable for investigating MASH-HCC mechanisms and therapeutic strategies.