Grøndahl-Hansen J, Hilsenbeck S G, Christensen I J, Clark G M, Osborne C K, Brünner N
Finsen Laboratory, Copenhagen, Denmark.
Breast Cancer Res Treat. 1997 Apr;43(2):153-63. doi: 10.1023/a:1005744914124.
Cancer cell invasion is accomplished by the concerted action of several extracellular proteolytic enzyme systems, one of which is the urokinase plasminogen activation system. The different components of this system. e.g. urokinase plasminogen activator (uPA), its receptor uPAR, as well as its main inhibitor plasminogen activator inhibitor type 1 (PAI-1) have all been shown to have prognostic value in breast cancer, i.e. high tumor levels are associated with a poor prognosis. In order to further substantiate the prognostic value of uPA and PAI-1, we have tested the cutpoints (median values and optimized outpoints) from our first study (Cancer Res 53: 2513-2521, 1993) in an independent group of breast cancer patients. Breast cancer cytosols from 100 premenopausal and 150 post-menopausal node positive patients were included. The median observation time was 80 months (range 49-145). Univariate analysis showed that high PAI-1 levels (above the median PAI-1 value) were significantly associated with short recurrence-free survival (RR: 1.65; 95% CI: 1.04-2.63; P = 0.03) and short overall survival (RR: 2.46; 95% CI: 1.52-3.96; P = 0.0001) in postmenopausal patients. Postmenopausal patients with high uPA levels (above the median uPA value) had a significantly shorter recurrence-free survival (RR: 2.04; 95% CI: 1.17-3.56; P = 0.01) and overall survival (RR: 2.07; 95% CI: 1.16-3.70; P = 0.01) than patients with low uPA values. Nearly identical results were obtained when using the optimized PAI-1 or uPA value. In a Cox multivariate analysis which included other established prognostic factors, high PAI-1 was found to be an independent prognostic variable predicting short overall survival with a relative risk of 2.27 in postmenopausal women, and high uPA was found to be an independent prognostic variable predicting short recurrence-free survival with a relative risk of 1.86 in postmenopausal women. The present study indicates that uPA and PAI-1 are independent and significant prognostic variables in subsets of breast cancer patients.
癌细胞侵袭是由几种细胞外蛋白水解酶系统协同作用完成的，其中之一是尿激酶纤溶酶原激活系统。该系统的不同组分，如尿激酶纤溶酶原激活剂（uPA）、其受体uPAR以及其主要抑制剂1型纤溶酶原激活剂抑制剂（PAI-1），均已显示在乳腺癌中具有预后价值，即肿瘤水平高与预后不良相关。为了进一步证实uPA和PAI-1的预后价值，我们在一组独立的乳腺癌患者中测试了我们第一项研究（《癌症研究》53: 2513 - 2521, 1993）中的切点（中位数和优化的外推值）。纳入了100例绝经前和150例绝经后淋巴结阳性患者的乳腺癌细胞溶质。中位观察时间为80个月（范围49 - 145个月）。单因素分析显示，在绝经后患者中，高PAI-1水平（高于PAI-1中位数）与无复发生存期短显著相关（风险比：1.65；95%置信区间：1.04 - 2.63；P = 0.03）以及总生存期短显著相关（风险比：2.46；95%置信区间：1.52 - 3.96；P = 0.0001）。uPA水平高（高于uPA中位数）的绝经后患者的无复发生存期（风险比：2.04；95%置信区间：1.17 - 3.56；P = 0.01）和总生存期（风险比：2.07；95%置信区间：1.16 - 3.70；P = 0.01）明显短于uPA值低的患者。使用优化的PAI-1或uPA值时获得了几乎相同的结果。在一项包括其他已确定的预后因素的Cox多因素分析中，发现高PAI-1是预测绝经后女性总生存期短的独立预后变量，相对风险为2.27，并且发现高uPA是预测绝经后女性无复发生存期短的独立预后变量，相对风险为1.86。本研究表明，uPA和PAI-1在部分乳腺癌患者中是独立且重要的预后变量。
