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.