CLINICAL IMPLICATIONS OF TUMOR ASSOCIATED PROTEASES DETERMINATIONIN THE TUMORS AND BLOOD PLASMA OF COLORECTAL CANCER PATIENTS

E.S. Gershtein, E.A. Korotkova, V.V. Prorokov, N.E. Kushlinskii
Federal State Budgetary Institution «The N.N. Blokhin Russian Cancer Research Center» of the Russian Academy of Medical Sciences, Moscow, Russian Federation

Associations between matrix metalloproteinase (MMP) 2, 7, 9, tissue MMP inhibitor TIMP-1 and plasminogen activation system components (uPA, tPA and PAI-1) plasma and/or tumor levels in colorectal cancer (CRC) patients were evaluated in order to reveal their potential clinical implications. Two groups of CRC patients monitored for 5 or 10 years were enclosed in the study. Earlier, corresponding markers’ levels were measured in their plasma and/or tumors by immunoenzymatic techniques. High tumor PAI-1 (≥4,0 ng/mg protein) was demonstrated to be a significant, but not independent unfavorable prognostic factor for 5 and 10 years overall survival. Its role was mostly pronounced in stage III patients. High preoperative plasma MMP-7 and TIMP-1 levels (cut-offs – 4,0 and 347 ng/ml respectively) were shown to be independent unfavorable prognostic factors, and univariate analysis revealed unfavorable prognostic value of high tumor MMP-7 content (≥7,8 ng/mg protein) in patients with disseminated process.
Keywords: 
urokinase type plasminogen activator (uPA), tissue type plasminogen activator (tPA), type 1 plasminogen activator inhibitor (PAI-1), matrix metalloproteinase 2, matrix metalloproteinase 7, matrix metalloproteinase 9, tissue matrix metalloproteinase inhibitor 1, colorectal cancer, prognosis