PROGNOSTIC VALUES OF CATHEPSIN-B AND CARCINOEMBRYONIC ANTIGEN IN SERAOF PATIENTS WITH COLORECTAL-CANCER

The level of cathepsin B (Cat B) was determined in sera obtained preop eratively from 325 patients with colorectal cancer using an ELISA, Con trol sera from 90 healthy blood donors were analyzed. The levels of Ca t B detected included all forms that were present in the sera, i.e., m ature enzyme, precursor molecule, and enzyme-inhibitor complexes. The level of Cat B was significantly increased in sera of patients with co lorectal cancer. The median level was 10.7 ng/ml versus 2.1 ng/ml in c ontrols (P < 0.0001). A correlation between Cat B serum level and adva nced Dukes' stage (P < 0.003) was found, whereas no associations have been found with age, sex, or level of carcinoembryonic antigen (CEA), In survival analysis, the patients with high serum Cat B experienced s ignificantly lower survival probability. At the optimal cutoff value o f 9.4 ng/ml, the relative hazard ratio was 1.8 (95% confidence interva l, 1.1-2.8; P = 0.016) in the univariate Cox proportional hazards mode l. The median observation time was 4.4 years (range, 3.2-5.5 years). I n multivariate analysis, Dukes' stage was the strongest prognostic var iable, followed by age, whereas serum Cat B and CEA were not significa nt prognostic factors in this model, in accordance with their associat ion with Dukes' stage. When the data for Cat B and CEA were combined, CEA-positive patients were further separated by Cat B into high-and lo w-risk groups. Patients with high serum levels of both molecules had s ignificantly shorter survival (relative hazard ratio of 2.2; 95% confi dence interval, 1.5-3.2; P < 0.0001), as compared with patients with l ow levels of both molecules.