Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: Relation to prognosis

The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystat in C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately i ncreased in patient sera (1,4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compar ed with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml fo r cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated sign ificantly with Dukes' stage, its level being the highest in stage D (P < 0. 007). Stefin B and cystatin C correlated with survival, whereas stefin A wa s not a significant prognostic factor in this study, Using medians as cutof f values, patients with high levels of stefin B and patients with high leve ls of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interv al, 1.0-1.8; P = 0.01 for cystatin C), Our results reveal a correlation bet ween high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support prev ious studies suggesting a contributing role of protease inhibitors in the p rogression of cancer.