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 cystatin 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 increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared 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 for 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 significantly 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 was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels 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 interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.
Kos
J
J
Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, Ljubljana, Slovenia. janko.kos@ijs.si
Krasovec
M
M
Cimerman
N
N
Nielsen
H J
HJ
Christensen
I J
IJ
Brünner
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D055312:Cystatin A; D055313:Cystatin B; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D015853:Cysteine Proteinase Inhibitors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012016:Reference Values; D012307:Risk Factors; D013997:Time Factors
D014408:Biomarkers, Tumor; C525030:CST3 protein, human; C524994:CSTB protein, human; D055312:Cystatin A; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; C026407:CSTA protein, human; D055313:Cystatin B