Dynamics and predicted drug response of a gene network linking dedifferentiation with β-catenin dysfunction in hepatocellular carcinoma

Background & Aims Alterations of individual genes variably affect the development of hepatocellular carcinoma (HCC). Thus, we aimed to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRNs). Methods Using data from The Cancer Genome Atlas, from the LIRI-JP (Liver Cancer – RIKEN, JP project), and from our transcriptomic, transfection and mouse transgenic experiments, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of β-catenin (CTNNB1). We further generated and validated a quantitative mathematical model of the GRN using human cell lines and in vivo expression data. Results We found that LIN28B and C…

Multidisciplinary strategies to improve treatment outcomes in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a complex disease with a poor prognosis. Incidence and mortality rates are increasing in many geographical regions, indicating a need for better management strategies. Among several risk factors for HCC, the most common are cirrhosis because of chronic hepatitis B virus or hepatitis C virus infection and alcohol consumption, obesity, and diabetes. In some patients, combined risk factors present additional challenges to the prevention and treatment of HCC. Screening and surveillance of high-risk populations varies widely by geographic regions, and access to optimal surveillance is critical for early diagnosis. The treatment choice for HCC depends on the canc…

Fighting the bushfire in HCC trials

Long-term Evolution of Hepatocellular Adenomas at MRI Follow-up.

Background Hepatocellular adenomas (HCAs) are rare benign liver tumors. Guidelines recommend continued surveillance of patients diagnosed with HCAs, but these guidelines are mainly based on small studies or expert opinion. Purpose To analyze the long-term evolution of HCAs, including solitary and multiple lesions, and to identify predictive features of progression with MRI. Materials and Methods In a retrospective study, patients diagnosed with pathologically proven solitary or multiple HCAs between January 2004 and December 2015 were included; β-catenin-mutated HCAs and HCAs with foci of malignancy were considered to be at risk for progression. MRI examinations were analyzed, and tumor evo…