Evaluation of Fbxw7 expression and its correlation with the expression of c-Myc, cyclin E and p53 in human hepatocellular carcinoma
Evaluation of Fbxw7 expression and its correlation with the expression of c-Myc, cyclin E and p53 in human hepatocellular carcinoma
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人肝细胞癌中Fbxw7表达及其与c-Myc、cyclin E、p53表达的相关性评价
DOI：
10.1111/j.1872-034x.2012.01005.x
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Liu, Qingguang
中科院分区：
文献类型：
--
作者：
Tu, Kangsheng;Zheng, Xin;Liu, Qingguang
目的：F-box and WD repeat domain-containing 7（Fbxw 7）是一个细胞周期调控基因，其作用靶点是c-Myc和cyclin E等多种细胞周期调控因子的泛素化和蛋白酶体降解。Fbxw 7基因的缺陷导致细胞周期重新进入并加速G1-S转换，被认为是癌症发展的原因之一。然而，它的表达和肝细胞癌（HCC）患者的临床意义仍然不确定。这促使我们研究其在HCC患者中的表达水平，以确定其临床意义。方法：收集60例手术切除的成对HCC和癌旁正常组织。逆转录聚合酶链反应和免疫组化检测Fbxw 7在mRNA和蛋白水平的表达。免疫组化检测c-Myc、cyclin E和p53蛋白表达与Fbxw 7的相关性。结果如下：肝癌组织中Fbxw 7的mRNA和蛋白表达均显著低于癌旁正常组织（P < 0.01）。fbxw 7蛋白在组织学分级高、淋巴结转移期晚的患者中表达明显降低。在肝癌组织中，Fbxw 7蛋白表达与c-Myc、cyclin E和p53呈负相关（分别为r =-0.459，P < 0.05; r =-0.573，P < 0.001; r =-0.579，P < 0.05）。结论：在HCC中，Fbxw 7表达降低与临床病理特征密切相关，并可能通过增强细胞周期调节蛋白的功能而具有预后潜力。
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 tumornodemetastasis 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.