lImpact of cyclins E, neutrophil elastase and proteinase 3 expression levels on clinical outcome in primary breast cancer patients
lImpact of cyclins E, neutrophil elastase and proteinase 3 expression levels on clinical outcome in primary breast cancer patients
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DOI：
10.1002/ijc.22149
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发表时间：
2006-12-01
影响因子：
6.4
通讯作者：
Sotiriou, Christos
中科院分区：
文献类型：
--
作者：
Desmedt, Christine;El Ouriaghli, Frank;Sotiriou, Christos
不受控制的细胞增殖是癌症的标志之一，从G1期到S期的转变是肿瘤中最常见的细胞周期异常。研究表明，G1期细胞周期蛋白E（CCNE）的致癌活性可通过弹性蛋白酶介导的蛋白水解加工产生高活性的低分子量形式（LMW）而放大。神经弹性蛋白酶（NE）和蛋白酶3（PR 3）是两种在乳腺癌细胞中异常表达的蛋白酶，似乎与细胞增殖有关。在这项研究中，我们评估了这2种蛋白酶的表达以及NE的2种潜在细胞内靶点（CCNE 1和CCNE 2）对205例原发性乳腺癌患者的临床结局的影响。经单因素分析，CCNE 1、CCNE 2、雌激素受体和分级对无复发间隔期（RFI）有显著预测作用。NE和PR 3未达到统计学显著性。在多变量分析中，CCNE 2升高[风险比（HR）2.10，p = 0.008]预测RFI缩短。在仅接受他莫昔芬治疗的患者的亚组分析中，高水平的CCNE 1预测治疗抵抗，而高水平的CCNE 2与未接受治疗的患者的不良RFI相关。研究CCNE 1、CCNE 2和NE之间的关系未显示对RFI有任何影响。总之，这项研究是第一个在一系列原发性乳腺癌患者中通过RT-PCR在mRNA水平上评估这些标志物的研究，我们的研究结果证实了高CCNE水平对全身性未治疗的早期乳腺癌患者的临床结果的影响，以及CCNE 1在仅接受他莫昔芬治疗的早期乳腺癌患者中的影响。(c)2006 Wiley-Liss，Inc.
Uncontrolled cell proliferation is one of the hallmarks of cancer and the transition from the G1 to S phase is the most commonly reported cell cycle abnormality in tumors. It has been shown that the oncogenic activity of G1 cyclin E (CCNE) can be amplified by generating hyperactive low molecular weight forms (LMW) through elastase-mediated proteolytic processing. Neutrophil elastase (NE) and proteinase 3 (PR3) are 2 proteases that are aberrantly expressed in breast cancer cells and seem to be involved in cell proliferation. In this study, we evaluated the effect of the expression of these 2 proteases in addition to 2 potential intracellular targets of NE (CCNE1 and CCNE2) on clinical outcome in a population of 205 primary breast cancer patients. By univariate analysis, CCNE1, CCNE2, estrogen receptor and grade significantly predicted relapse free interval (RFI). NE and PR3 did not achieve statistical significance. In a multivariate analysis, elevated CCNE2 [hazard ratio (HR) 2.10, p = 0.008] predicted shorter RFI. In subgroup analyses of the tamoxifen-only treated patients, high CCNE1 levels predicted treatment resistance, while high levels of CCNE2 were associated with poor RFI in untreated patients. Investigation of the relationship between CCNE1, CCNE2 and NE did not show any impact on RFI. To conclude, this study was the first to evaluate these markers at the mRNA level by RT-PCR in a series of primary breast cancer patients, and our results confirmed the impact of high CCNE levels on clinical outcome in systemically untreated and of CCNE1 in tamoxifen-only treated early breast cancer patients. (c) 2006 Wiley-Liss, Inc.