Significance of Skp2 expression in primary breast cancer
Significance of Skp2 expression in primary breast cancer
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DOI：
10.1158/1078-0432.ccr-05-1709
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发表时间：
2006-02-15
影响因子：
11.5
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Sonoda, H;Inoue, H;Mori, M
目的：我们以前报道p27表达水平是一个独立的预后因素，高S期激酶相关蛋白2（Skp 2）表达水平与胃癌患者预后不良显著相关。我们在此研究了Skp 2在乳腺癌中的表达，并试图确定Skp 2的表达状态和临床病理变量或患者的预后之间的任何关联。实验设计：我们建立了四个Skp 2转染的乳腺癌细胞系，并评估了Skp 2和p27表达之间的相关性，使用实时逆转录-PCR和Western印迹分析。然后，我们分析了169例日本乳腺癌患者Skp 2 mRNA表达的临床病理意义。结果：Skp 2转染后，p27蛋白表达明显下降，而p27 mRNA表达无明显变化。Skp 2蛋白表达水平与Skp 2 mRNA表达水平呈显著相关（P = 0.001），与p27蛋白表达水平呈显著负相关（P = 0.042）。Skp 2基因高表达的患者明显年轻于低表达的患者（P = 0.002）。Skp 2高表达患者的预后显著差于低表达患者（P = 0.022）。此外，Skp 2的高表达是与较短的无病生存期相关的独立变量（相对危险度，3.33; 95%可信区间，1.296-8.578; P = 0.013）。目前的结果表明，Skp 2可能发挥重要作用，特别是在年轻乳腺癌，并且它也被认为具有很强的独立预后潜力，因此可以证明是治疗乳腺癌的有用靶点。
Purpose: We previously reported the p27 expression level to be an independent prognostic factor, and a high S-phase kinase-associated protein 2 (Skp2) expression level was significantly correlated with a poor prognosis in patients with gastric cancer. We herein examined the Skp2 expression in breast cancer and attempted to identify any associations between the Skp2 expression status and either the clinicopathologic variables or the patient's prognosis.Experimental Design: We established four Skp2-transfected breast cancer cell lines and assessed the correlations between the Skp2 and p27 expressions using real-time reverse transcription-PCR and a Western blot analysis. We then analyzed the clinicopathologic significance of Skp2 mRNA expression in 169 Japanese patients with breast cancer. An immunohistochemical analysis was also done.Results: The p27 protein expression markedly decreased after Skp2 transfection, whereas no alteration in the p27 m RNA expression was observed. The Skp2 protein expression level as determined by immunohistochemical staining thus showed a significant correlation with the Skp2 mRNA expression (P = 0.001) and a significant inverse correlation with the p27 protein expression (P = 0.042). The patients with a high Skp2 gene expression were significantly younger than those with a low expression (P = 0.002). The prognosis of patients with a high Skp2 expression was significantly (P = 0.022) poorer than for those with a low expression. Moreover, a high expression of Skp2 was an independent variable that correlated with a shorter disease-free survival (relative risk, 3.33; 95% confidence interval, 1.296-8.578; P = 0.013).Conclusions: The present results suggest that Skp2 may play an important role particularly in young breast cancer, and it is also considered to have strong independent prognostic potential and thus may prove to be a useful target for the treatment of breast cancer.