Nekarda H, Schmitt M, Ulm K, Wenninger A, Vogelsang H, Becker K, Roder J D, Fink U, Siewert J R
Chirurgische Klinik und Poliklinik, Technische Universität München, Germany.
Cancer Res. 1994 Jun 1;54(11):2900-7.
The prognostic impact of the proteolytic factors urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) was evaluated in 76 completely resected gastric cancer patients enrolled in a prospective study. All patients underwent macroscopically and microscopically residual tumor-free resection (category R0, Union International Contre Cancer, 1987). uPA and PAI-1 levels were quantified in detergent-extracted (Triton X-100) specimens of primary gastric tumors by enzyme-linked immunosorbent assays. Median values of 1.57 ng uPA/mg protein were determined in tumor tissue extracts compared to 0.14 ng uPA/mg protein in normal mucosa. For PAI-1, 0.93 ng PAI-1/mg protein versus 0.09 ng PAI-1/mg protein was calculated. uPA levels in tumor tissue extracts were significantly correlated with vascular invasion, Laurén classification, and WHO classification, whereas PAI-1 levels showed a significant correlation with advanced lymph node involvement, depth of invasion, tumor stage, site of tumor, and the Laurén, Borrmann, and WHO classifications. Elevated uPA and PAI-1 levels were found to be associated with poor prognosis. The optimal cutoff values indicating a group of patients with shorter survival were 1.5 ng uPA/mg protein and 1.25 ng PAI-1/mg protein, respectively (Classification and Regression Tree analysis). Patients with either high uPA or PAI-1 values were significantly associated with decreased survival (median time of survival was 23 months (high) versus 44 months (low). By univariate Cox regression analysis, it was shown that TNM categories, WHO classification, size of tumor, uPA and PAI-1 levels were all significantly associated with survival. However, in multivariate Cox regression analysis of these grouped variables, nodal status, PAI-1 levels, and WHO classification were the only independent prognostic factors. The relative risks of failure were 5-, 2.9-, and 2.4-fold, respectively. We conclude that PAI-1 and uPA positivity may serve as new prognostic factors in gastric cancer, predicting shorter survival even in clinically important subgroups of patients.
在一项前瞻性研究纳入的76例接受了完全切除的胃癌患者中，评估了蛋白水解因子尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂1型（PAI-1）的预后影响。所有患者均接受了宏观和微观上无残留肿瘤的切除（R0分类，国际抗癌联盟，1987年）。通过酶联免疫吸附测定法对原发性胃肿瘤的去污剂提取物（Triton X-100）样本中的uPA和PAI-1水平进行定量。肿瘤组织提取物中uPA的中位数为1.57 ng uPA/mg蛋白，而正常黏膜中为0.14 ng uPA/mg蛋白。对于PAI-1，计算得出肿瘤组织提取物中为0.93 ng PAI-1/mg蛋白，正常黏膜中为0.09 ng PAI-1/mg蛋白。肿瘤组织提取物中的uPA水平与血管侵犯、Laurén分类和世界卫生组织（WHO）分类显著相关，而PAI-1水平与晚期淋巴结受累、浸润深度、肿瘤分期、肿瘤部位以及Laurén、Borrmann和WHO分类显著相关。发现uPA和PAI-1水平升高与预后不良相关。表明一组生存期较短患者的最佳临界值分别为1.5 ng uPA/mg蛋白和1.25 ng PAI-1/mg蛋白（分类与回归树分析）。uPA或PAI-1值高的患者与生存期缩短显著相关（生存期中位数为23个月（高）对44个月（低））。通过单因素Cox回归分析表明，TNM分类、WHO分类、肿瘤大小、uPA和PAI-1水平均与生存期显著相关。然而，在对这些分组变量进行多因素Cox回归分析时，淋巴结状态、PAI-1水平和WHO分类是仅有的独立预后因素。失败的相对风险分别为5倍、2.9倍和2.4倍。我们得出结论，PAI-1和uPA阳性可能作为胃癌新的预后因素，即使在临床上重要的患者亚组中也能预测生存期较短。
