Molecular characterization of long-term survivors of hepatocellular carcinoma

Hepatocellular carcinoma is one of the most fatal cancers, and the majority of patients die within three years. However, a small proportion of patients overcome this fatal disease and survive for more than five years. To determine the molecular characteristics of long-term survivors (survival ≥ 5 years), we analyzed the genomic and clinical data of hepatocellular carcinoma patients from The Cancer Genome Atlas and the International Cancer Genome Consortium databases, and identified molecular features that were strongly associated with the patients’ prognosis. Genes involved in the cell cycle were expressed at lower levels in tumor tissues from long-term survivors than those from short-term survivors (survival ≤ 1 years). High levels of positive regulators of the G₁/S cell cycle transition (cyclin-dependent kinase 2 [CDK2], CDK4, Cyclin E2 [CCNE2], E2F1, E2F2) were potential markers of poor prognosis. Hepatocellular carcinoma patients with TP53 mutations were mainly belonged to the short-term survivor group. Abemaciclib, an FDA-approved selective inhibitor of CDK4/6, inhibited the cell proliferation and tumor growth of hepatocellular carcinoma cells in vitro and in vivo. Thus, high G₁/S transition-related gene levels and TP53 mutations are promising diagnostic biomarkers for short-term survivals, and abemaciclib may be a potential targeted drug for hepatocellular carcinoma.