Untitled ItemG1/S transition with mutant p53 as prognostic indicators and therapeutic targets for hepatocellular carcinoma

Objectives: The traditional pathologic and histologic diagnosis is very effective for cancer prognostic prediction,such as lung cancer and colorectal cancer. However, for hepatocellular carcinoma (HCC), the second-deadliest cancer, the effects are very limit. Materials and Methods: To identify novel biomarkers for outcome prediction and therapeutic targets, we compared the global gene expression of primary HCC samples between long-term survivors (LTSs) and short-term survivors (STSs) in TCGA database. We also explored the association between TP53 mutational and patients’ prognosis. Finally, we validated the identified novel molecular biomarkers with databases and experiments. Results: Genes involved in cell cycle were upregulated significantly in STS HCC tissues. The high expressions of eight positive regulators of G1/S cell cycle transition were closely associated with patients’ poor prognosis. In addition, patients with TP53 mutations, usually with highly expressing cell cycle genes, exhibited STSs. Meanwhile, we identified that patients with both mutant TP53 and high expression of five positive regulators of G1/S cell cycle transition exhibited a poor survival probability. Finally, we demonstrated that palbociclib significantly inhibited the cell proliferation of HCC cells with p53 mutation. Conclusions: The expression of five positive regulators of G1/S transition with TP53 mutation are promising prognostic molecular biomarkers for STSs HCC patients and these people are the potential target patients of a rationale CDK4/6 inhibitor therapy.