Expression of Urokinase-Type Plasminogen Activator (uPA), its Receptor (uPAR), and Inhibitor (PAI-1) in Human Breast Carcinomas and Their Clinical Relevance
Expression of Urokinase-Type Plasminogen Activator (uPA), its Receptor (uPAR), and Inhibitor (PAI-1) in Human Breast Carcinomas and Their Clinical Relevance
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DOI：
10.1002/jcla.21488
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Wittliff, James L.
中科院分区：
文献类型：
--
作者：
Andres, Sarah A.;Edwards, Angelena B.;Wittliff, James L.
丝氨酸蛋白酶将纤溶酶原转化为纤溶酶，纤溶酶参与生理和病理生理条件下的组织重塑，包括乳腺癌的侵袭和进展。尿激酶型纤溶酶原激活剂 (uPA) 和 uPA 前体均与靶细胞上的 uPA 受体 (uPAR) 相关，其中纤溶酶原激活剂抑制剂（例如 PAI-1）可以调节其活性。将这些因子在乳腺癌中的表达水平与患者特征、癌症特征和临床结果进行比较。通过酶联免疫吸附测定 (ELISA) 对 226 个活检组织提取物中的 uPA、uPAR 和 PAI-1 进行定量，同时通过酶免疫测定 (EIA) 或放射性配体结合测定雌激素受体 (ER) 和孕激素受体 (PR)。每组测定均包含一个新颖的参考样本，其中这五种分析物的含量均已知。这些生物标志物的 ng/mg 蛋白质水平表现出以下范围：uPA (0-12.3)； uPAR（0-19.5）； PAI-1 (0-91.2)。独立考虑时，uPA、uPAR 或 PAI-1 的表达与患者年龄或绝经状态无关。尽管没有观察到每种分析物与分期、分级或 ER/PR 状态之间的相关性，但水平似乎随病理学和淋巴结状态而不同。 106 个样本中 uPA、uPAR 和 PAI-1 水平的层次聚类树状图揭示了三组乳腺癌患者。 uPA、uPAR 和 PAI-1 的 Kaplan-Meier 分析表明与总生存期 (OS) 相关，表明对这些生物标志物的集体检查有助于预测乳腺癌的临床结果。 J.克林。实验室。肛门。 26:93-103, 2012。(C) 2012 Wiley 期刊公司。
Serine proteases convert plasminogen to plasmin which is involved in tissue remodeling under physiologic and pathophysiologic conditions, including breast carcinoma invasion and progression. Both urokinase-type plasminogen activator (uPA) and pro-uPA associate with uPA receptor (uPAR) on target cells, where plasminogen activator inhibitors (e.g., PAI-1) may modulate their activities. Expression levels of these factors were compared in breast carcinomas relative to patient characteristics, carcinoma features, and clinical outcome. uPA, uPAR, and PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA) in extracts of 226 biopsies while estrogen receptor (ER) and progestin receptor (PR) were determined by enzyme immunoassay (EIA) or radio-ligand binding. Each set of assays contained a novel reference specimen with known quantities of each of these five analytes. Levels in ng/mg protein of these biomarkers exhibited ranges: uPA (0-12.3); uPAR (0-19.5); PAI-1 (0-91.2). When considered independently, expression of uPA, uPAR, or PAI-1 was unrelated to patient age or menopausal status. Although no correlation was observed between each analyte with stage, grade, or ER/PR status, levels appeared to differ with pathology and nodal status. A dendrogram from hierarchical clustering of uPA, uPAR, and PAI-1 levels in 106 specimens revealed three clusters of breast cancer patients. Kaplan-Meier analyses of uPA, uPAR, and PAI-1 indicated a correlation with overall survival (OS), suggesting collective examination of these biomarkers is useful in predicting clinical outcome of breast cancer. J. Clin. Lab. Anal. 26:93-103, 2012. (C) 2012 Wiley Periodicals, Inc.