Association between preoperative plasma levels of tissue inhibitor of metalloproteinases 1 and rectal cancer patient survival: a validation study

Abstract

The level of the tissue inhibitor of metalloproteinases 1 (TIMP-1) has previously been demonstrated to predict the survival of early stage colorectal cancer patients. The present study was undertaken to further validate plasma TIMP-1 as a prognostic marker in rectal cancer. Preoperative plasma from 352 rectal cancer patients were analysed using an immunoassay for TIMP-1. The TIMP-1 immunoassay demonstrated robustness and good reproducibility with low interassay coefficients of variation (CV). The rectal cancer patients had a mean plasma TIMP-1 level of 184 μg/l (standard deviation (SD): 70 μg/l). There were no significant differences in TIMP-1 levels between patients with Dukes’ stage A, B or C disease, whereas Dukes’ stage D patients had significantly increased TIMP-1 levels (P<0.0001); however, high levels of TIMP-1 were not restricted to those with advanced disease. Univariate analysis demonstrated an increasing risk of mortality with increasing TIMP-1 levels Hazard Ratio (HR)=2.9; 95% Confidence Interval (CI): 1.7–5.0; P<0.0001). Including additional covariates, multivariate analysis identified plasma TIMP-1 as an independent prognostic marker (HR=2.2; 95% CI: 1.2–4.1 (P=0.01). This study showed a highly significant and independent association between preoperative plasma TIMP-1 levels and survival in rectal cancer patients, thus confirming our previous findings. Furthermore, the TIMP-1 immunoassay proved to be stable and reproducible in this confirmatory study.