Kushlinskii N E, Gershtein E S, Korotkova E A, Prorokov V V
N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
Bull Exp Biol Med. 2013 Jan;154(3):365-9. doi: 10.1007/s10517-013-1952-4.
The relationship between the tumor and plasma levels of tumor-associated proteases - components of plasminogen activation system (uPA, tPA, and PAI-1), matrix metalloproteinases (MMP) 2, 7, 9 and their inhibitor (TIMP-1) - and the survival rate of patients with colorectal cancer was analyzed in order to evaluate the clinical significance of these markers. The study was carried out in two groups of patients, observed for 5 and 10 years, in whom the levels of these proteins were previously measured by enzyme immunoassays. High level of PAI-1 in the tumor (≥4.0 ng/mg protein) was found to be a significant, but not independent unfavorable prognostic factor for overall 5- and 10-year survival. The role of this factor was mainly significant in patients with stage III disease. High preoperative plasma levels of MMP-7 and TIMP-1 (threshold values 4.0 and 347 ng/ml, respectively) were independent unfavorable prognostic factors, while in unifactorial analysis, high level of MMP-7 (≥7.8 ng/mg protein) in the tumors of patients with disseminated process was olso an unfavorable prognostic factor.
为评估这些标志物的临床意义，分析了肿瘤与血浆中肿瘤相关蛋白酶（纤溶酶原激活系统的组成成分，即尿激酶型纤溶酶原激活物（uPA）、组织型纤溶酶原激活物（tPA）和纤溶酶原激活物抑制剂-1（PAI-1））、基质金属蛋白酶（MMP）2、7、9及其抑制剂（TIMP-1）水平之间的关系，以及它们与结直肠癌患者生存率的关系。该研究在两组患者中进行，观察期分别为5年和10年，此前已通过酶免疫测定法检测了这些蛋白质的水平。发现肿瘤中PAI-1水平高（≥4.0 ng/mg蛋白质）是5年和10年总生存率的一个显著但非独立的不良预后因素。该因素的作用在III期疾病患者中尤为显著。术前血浆中MMP-7和TIMP-1水平高（阈值分别为4.0和347 ng/ml）是独立的不良预后因素，而在单因素分析中，有播散性病变患者的肿瘤中MMP-7水平高（≥7.8 ng/mg蛋白质）也是一个不良预后因素。
