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

<b>Objectives: </b>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. <b>Materials and Methods:</b><b> </b>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 <i>TP53</i> mutational and patients’ prognosis. Finally, we validated the identified novel molecular biomarkers with databases and experiments. <b>Results: </b>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 <i>TP53</i> mutations, usually with highly expressing cell cycle genes, exhibited STSs. Meanwhile, we identified that patients with both mutant <i>TP53</i> 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. <b>Conclusions: </b>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 <i>CDK4/6</i> inhibitor therapy.