Révillion Françoise, Puech Carole, Rabenoelina Fanja, Chalbos Dany, Peyrat Jean-Philippe, Freiss Gilles
Contrôle de la progression des cancers hormono-dépendants, Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret, Lille, France.
Int J Cancer. 2009 Feb 1;124(3):638-43. doi: 10.1002/ijc.23989.
Although it is well established that some protein tyrosine kinases have a prognostic value in breast cancer, the involvement of protein tyrosine phosphatases (PTPs) is poorly substantiated for breast tumors. Three of these enzymes (PTP-gamma, LAR, and PTPL1) are already known to be regulated by estrogens or their antagonists in human breast cancer cells. We used a real-time reverse transcriptase polymerase chain reaction method to test the expression levels of PTP-gamma, LAR and its neuronal isoform, and PTPL1 in a training set of RNA from 59 breast tumors. We sought correlations between levels of these molecular markers, current tumor markers, and survival. We then quantified the expression level of the selected phosphatase in 232 additional samples, resulting in a testing set of 291 breast tumor RNAs from patients with a median follow-up of 6.4 years. The Spearman nonparametric test revealed correlations between PTPL1 expression and differentiation markers. Cox univariate analysis of the overall survival studies demonstrated that PTPL1 is a prognostic factor [risk ratio (RR)=0.45], together with the progesterone receptor (PR) (RR=0.52) and node involvement (RR=1.58). In multivariate analyses, PTPL1 and PR retained their prognostic value (RRs of 0.48 and 0.55, respectively). This study demonstrates for the first time that PTPL1 expression level is an independent prognostic indicator of favorable outcome for patients with breast cancer. In conjunction with our mechanistic studies, this finding identifies PTPL1 as an important regulatory element of human breast tumor aggressiveness and sensitivity to treatments such as antiestrogens and antiaromatase.
虽然已有充分证据表明某些蛋白酪氨酸激酶在乳腺癌中具有预后价值，但蛋白酪氨酸磷酸酶（PTP）在乳腺肿瘤中的作用却缺乏充分的证据支持。已知其中三种酶（PTP-γ、LAR和PTPL1）在人乳腺癌细胞中受雌激素或其拮抗剂调控。我们使用实时逆转录聚合酶链反应方法检测了59例乳腺肿瘤RNA训练集中PTP-γ、LAR及其神经元异构体和PTPL1的表达水平。我们探寻了这些分子标志物水平、现有肿瘤标志物与生存率之间的相关性。然后我们对另外232个样本中所选磷酸酶的表达水平进行了定量，从而形成了一个包含291例乳腺肿瘤RNA的测试集，这些患者的中位随访时间为6.4年。Spearman非参数检验揭示了PTPL1表达与分化标志物之间的相关性。对总生存研究的Cox单变量分析表明，PTPL1是一个预后因素[风险比（RR）=0.45]，与孕激素受体（PR）（RR=0.52）和淋巴结受累情况（RR=1.58）一样。在多变量分析中，PTPL1和PR保留了它们的预后价值（RR分别为0.48和0.55）。本研究首次证明PTPL1表达水平是乳腺癌患者预后良好的独立预后指标。结合我们的机制研究，这一发现确定PTPL1是人类乳腺肿瘤侵袭性以及对抗雌激素和芳香化酶抑制剂等治疗敏感性的重要调节元件。
