The tumor marker and prognostic impact of cathepsin B, cathepsin L, urokinase-type plasminogen activator and its inhibitor type-1 in colorectal cancer

Background: Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 play an important part in colorectal cancer invasion. The tumor marker and prognostic impact of these proteases has not been evaluated in the same experimental setting, and compared with that of CEA and CA-19-9. Methods: Protease, CEA, CA 19-9 serum or plasma levels were determined in 56 patients with colorectal cancer, 25 patients with ulcerative colitis, 26 patients with colorectal adenomas and 35 tumor-free control patients. Protease, CEA, CA 19-9 levels have been determined by ELISA and electrochemiluminescence immunoassay, respectively; their sensitivity, specificity, diagnostic accuracy have been calculated and correlated with clinicopathological staging. Results: The proteases antigen levels were significantly higher in colorectal cancer than in other groups. Sensitivity of PAI-1 (94%), CATB (82%), UPA (69%), CATL (41%) were higher than those of CEA or CA 19-9 (30% and 18%, respectively). PAI-1, CATB and UPA demonstrated a better diagnostic accuracy than CEA or CA 19-9. A combination of PAI-1 with CATB or UPA exhibited the highest sensitivity value (98%). High CATB, PAI-1, CEA, CA 19-9 levels correlated with advanced Dukes stages. CATB (P=0.0004), CATL (P=0.02) and PAI-1 (P=0.01) had a significant prognostic impact. CATB proved the only Dukesindependent predictor variable for survival (P=0.02). Conclusions: At the time of clinical detection proteases are more sensitive indicators for colorectal cancer than the commonly used tumor markers. Our results may indicate the benefit of multiparametric tumor marker analyses for the diagnosis of colorectal cancer. Determinations of CATB, CATL and PAI-1 have a major prognostic impact in patients with colorectal cancer.