Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients
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DOI：
10.1093/jnci/94.2.116
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发表时间：
2002-01-16
影响因子：
10.3
通讯作者：
Foekens, JA
中科院分区：
文献类型：
--
作者：
Look, MP;van Putten, WLJ;Foekens, JA
背景：尿激酶型纤溶酶原激活物(UPA)及其抑制物(PAI-1)在肿瘤侵袭转移中起重要作用。高水平的uPA和PAT-1与乳腺癌患者的不良预后有关。为了确认uPA和PAI-1在原发性乳腺癌中的预后价值，我们重新分析了由欧洲癌症受体和生物标记物研究和治疗组织(EORTC-RBG)成员提供的个体患者数据。方法：这项研究包括18个数据集，涉及8377名乳腺癌患者。在随访期间(中位数79个月)，35%的患者复发，27%的患者死亡。肿瘤组织提取物中uPA和PAI-1的水平通过不同的免疫分析方法确定；数值在每个数据集中进行排序，并除以该数据集中的患者数量，以产生可以直接在数据集中进行比较的分数排序。对uPA和PAI-1水平与无复发生存期(RFS)和总生存期(OS)的关系进行COX多元回归分析，包括年龄、绝经状态、淋巴结状态、肿瘤大小、组织学分级和类固醇激素受体状态。所有P值均为双侧。结果：在所有患者的分析中，除淋巴结状况外，高水平的uPA和PAI-1是RFS差和OS差的最强预测因子。此外，在淋巴结阳性和淋巴结阴性的患者中，uPA和PAI-1的值较高独立地与RFS和OS差相关。尤其对于(未经治疗的)淋巴结阴性患者，uPA和PAI-1联合检测具有较强的预后能力(均P
Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph nodenegative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P