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 tissu e inhibitor of metalloproteinase (TIMP)-1 levels in colorectal cancer patie nts and relate these values to clinical and biochemical patient characteris tics. TIMP-1 levels were determined by ELISA in EDTA plasma samples collect ed preoperatively from 588 colorectal cancer patients. Plasma TIMP-1 levels were distributed with a median value of 141.1 mug/liter (range, 53.7-788.7 mug/liter). Whereas no significant differences were found in the median pl asma TIMP-1 levels among patients with Dukes' stage A, B, and C disease, pa tients with Dukes' stage D disease had significantly higher plasma TIMP-1 l evels (P < 0.0001); however, high plasma TIMP-1 levels were not restricted to advanced disease. A relatively weak correlation between plasma TIMP-1 le vel and age was found (r = 0.35; P < 0.0001), There was no significant diff erence in TIMP-1 levels between males and females (P = 0.97), Univariate an alysis demonstrated an increasing risk of mortality with increasing TIMP-1 levels [scored as the log,(TIMP-1); hazard ratio 33; 95% confidence interva l, 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 inter val, 1.7-3.7; P < 0.0001), This study showed a highly significant associati on between preoperative plasma TIMP-1 levels and survival in colorectal can ter patients, with higher plasma TIMP-1 levels being associated with poor o utcome, independent of clinical parameters including Dukes' stage, plasma T IMP-1 levels were found to strongly predict prognosis of colorectal ranter patients. Additional studies are needed to validate the clinical usefulness of plasma TIMP-1 measurements.