Prognostic Role of Tumor-Associated Proteases in Colorectal Cancer

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.