Evaluation of Fbxw7 expression and its correlation with the expression of c-Myc, cyclin E and p53 in human hepatocellular carcinoma

Aim: F-box and WD repeat domain-containing 7 (Fbxw7) is a cell cycle regulatory gene that targets for ubiquitination and proteasomal degradation various cell cycle regulators such as c-Myc and cyclin E. Defects in the Fbxw7 gene that lead to cell cycle re-entry and expedite the G1-S transition is thought to be one of the causes of cancer development. However, its expression and clinical importance for hepatocellular carcinoma (HCC) patients remains undetermined. This prompted us to investigate its expression level in HCC patients to establish its clinical significance. Methods: Sixty surgically resected paired HCC and normal tumor-adjacent tissues were freshly collected. Fbxw7 expression at both mRNA and protein level was examined by reverse transcription polymerase chain reaction and immunohistochemistry. The protein expression of c-Myc, cyclin E and p53 was evaluated by immunohistochemistry to identify correlations with Fbxw7. Results: The mRNA and protein expression of Fbxw7 was significantly downregulated in the HCC tumor tissues compared to the normal tumor-adjacent tissues (P<0.01, respectively). Fbxw7 protein was expressed at significantly lower levels in patients with high histological grade and advanced tumor-node-metastasis stage. In HCC tissues, Fbxw7 protein expression was negatively correlated with c-Myc, cyclin E and p53 (r=-0.459, P<0.05; r=-0.573, P<0.001; r=-0.579, P<0.05, respectively). Conclusion: In HCC, reduced Fbxw7 expression closely correlated with clinicopathological characteristics and may have prognostic potential through the enhanced function of cell cycle regulatory proteins.