High preoperative plasma tissue inhibitor of metalloproteinase-1 levels are associated with short survival of patients with colorectal cancer.
The objective of the present study was to measure preoperative plasma tissue inhibitor of metalloproteinase (TIMP)-1 levels in colorectal cancer patients and relate these values to clinical and biochemical patient characteristics. TIMP-1 levels were determined by ELISA in EDTA plasma samples collected preoperatively from 588 colorectal cancer patients. Plasma TIMP-1 levels were distributed with a median value of 141.1 microg/liter (range, 53.7-788.7 microg/liter). Whereas no significant differences were found in the median plasma TIMP-1 levels among patients with Dukes' stage A, B, and C disease, patients with Dukes' stage D disease had significantly higher plasma TIMP-1 levels (P < 0.0001); however, high plasma TIMP-1 levels were not restricted to advanced disease. A relatively weak correlation between plasma TIMP-1 level and age was found (r = 0.35; P < 0.0001). There was no significant difference in TIMP-1 levels between males and females (P = 0.97). Univariate analysis demonstrated an increasing risk of mortality with increasing TIMP-1 levels [scored as the log(e)(TIMP-1); hazard ratio = 3.3; 95% confidence interval, 2.6-4.2; P < 0.0001]. Including covariates (Dukes' stage, primary tumor location, gender, age, plasminogen activator inhibitor type 1, and soluble urokinase plasminogen activator receptor) in a multivariate analysis, TIMP-1 was retained in the final model (hazard ratio = 2.5; 95% confidence interval, 1.7-3.7; P < 0.0001). This study showed a highly significant association between preoperative plasma TIMP-1 levels and survival in colorectal cancer patients, with higher plasma TIMP-1 levels being associated with poor outcome. Independent of clinical parameters including Dukes' stage, plasma TIMP-1 levels were found to strongly predict prognosis of colorectal cancer patients. Additional studies are needed to validate the clinical usefulness of plasma TIMP-1 measurements.
Holten-Andersen
M N
MN
Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Stephens
R W
RW
Nielsen
H J
HJ
Murphy
G
G
Christensen
I J
IJ
Stetler-Stevenson
W
W
Brünner
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D017395:Plasminogen Activator Inhibitor 1; D019715:Tissue Inhibitor of Metalloproteinase-1