Widschwendter Andreas, Tonko-Geymayer Sibylle, Welte Thomas, Daxenbichler Günter, Marth Christian, Doppler Wolfgang
Department of Obstetrics and Gynecology and Institute of Medical Chemistry and Biochemistry University of Innsbruck, A-6020 Innsbruck, Austria.
Clin Cancer Res. 2002 Oct;8(10):3065-74.
Signal transducers and activators of transcription (STATs)were shown to be activated in mammary carcinoma. Because different STAT factors are likely to have different functions in these tumors, an assessment of their individual role is mandatory.
In this study we have separately determined activation of STAT1, STAT3, and STAT5 by measuring their DNA binding activity and tyrosine phosphorylation in breast cancer tissue samples. The predictive value of STAT activation on relapse-free and overall survival among women who received treatment for primary breast cancer was evaluated in a retrospective study.
Survival analysis demonstrated that patients with high STAT1 activation have substantially longer overall and relapse-free survival, irrespective of whether STAT1 activation was determined by its DNA binding activity (P = 0.003 and 0.010, respectively) or by its tyrosine phosphorylation (P = 0.046 and 0.011, respectively). In accordance, Cox proportional hazard regression analysis revealed an enhanced hazard of death (hazard ratio, 3.77; P = 0.018) and relapse of disease (hazard ratio, 6.55; P = 0.013) for the group of women with low STAT1 activation. After adjusting for known prognostic variables (lymph node status, stage of disease, estrogen receptor status, and cathepsin D), STAT1 activation remained an independent prognostic value. Activation of STAT3 and STAT5 DNA binding did not significantly correlate with prognosis.
Our study reveals a favorable and independent prognostic significance of STAT1 activation in mammary carcinoma, and is in accordance with the documented role of STAT1 in growth arrest, and in pro-apoptotic signaling pathways.
信号转导子和转录激活子（STATs）已被证明在乳腺癌中被激活。由于不同的STAT因子在这些肿瘤中可能具有不同的功能，因此必须评估它们各自的作用。
在本研究中，我们通过测量乳腺癌组织样本中STAT1、STAT3和STAT5的DNA结合活性和酪氨酸磷酸化，分别确定了它们的激活情况。在一项回顾性研究中，评估了STAT激活对接受原发性乳腺癌治疗的女性无复发生存率和总生存率的预测价值。
生存分析表明，STAT1激活水平高的患者总体生存期和无复发生存期显著更长，无论STAT1激活是通过其DNA结合活性（分别为P = 0.003和0.010）还是通过其酪氨酸磷酸化（分别为P = 0.046和0.011）来确定。相应地，Cox比例风险回归分析显示，STAT1激活水平低的女性组死亡风险增加（风险比，3.77；P = 0.018）和疾病复发风险增加（风险比，6.55；P = 0.013）。在调整已知的预后变量（淋巴结状态、疾病分期、雌激素受体状态和组织蛋白酶D）后，STAT1激活仍然是一个独立的预后价值指标。STAT3和STAT5 DNA结合的激活与预后没有显著相关性。
我们的研究揭示了STAT1激活在乳腺癌中具有良好的独立预后意义，这与文献记载的STAT1在生长停滞和促凋亡信号通路中的作用一致。
