Karin Michael, Kim Ju Youn
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Department of Molecular and Life Science, Hanyang University ERICA, Ansan, Korea.
Mol Oncol. 2025 Feb;19(2):275-294. doi: 10.1002/1878-0261.13685. Epub 2024 Jun 14.
Hepatocellular carcinoma is one of the deadliest and fastest-growing cancers. Among HCC etiologies, metabolic dysfunction-associated fatty liver disease (MAFLD) has served as a major HCC driver due to its great potential for increasing cirrhosis. The obesogenic environment fosters a positive energy balance and results in a continuous rise of obesity and metabolic syndrome. However, it is difficult to understand how metabolic complications lead to the poor prognosis of liver diseases and which molecular mechanisms are underpinning MAFLD-driven HCC development. Thus, suitable preclinical models that recapitulate human etiologies are essentially required. Numerous preclinical models have been created but not many mimicked anthropometric measures and the course of disease progression shown in the patients. Here we review the literature on adipose tissues, liver-related HCC etiologies and recently discovered genetic mutation signatures found in MAFLD-driven HCC patients. We also critically review current rodent models suggested for MAFLD-driven HCC study.
肝细胞癌是最致命且发展最快的癌症之一。在肝癌病因中，代谢功能障碍相关脂肪性肝病（MAFLD）因其极大的增加肝硬化的可能性，已成为肝癌的主要驱动因素。致肥胖环境促进正能量平衡，导致肥胖和代谢综合征持续增加。然而，很难理解代谢并发症如何导致肝脏疾病的不良预后，以及哪些分子机制支撑着MAFLD驱动的肝癌发展。因此，本质上需要合适的能够概括人类病因的临床前模型。已经创建了许多临床前模型，但很少有模型模拟人体测量指标以及患者所表现出的疾病进展过程。在此，我们综述了关于脂肪组织、肝脏相关肝癌病因以及最近在MAFLD驱动的肝癌患者中发现的基因突变特征的文献。我们还对目前建议用于MAFLD驱动的肝癌研究的啮齿动物模型进行了批判性综述。
