Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: A prospective validation study

Abstract

Background Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC. Patients and methods During 2000–2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms. Results High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6–2.7) and CEA (HR 1.2; 95% CI 1.1–1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5–2.6) and CEA (HR 1.2; 95% CI: 1.1–1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3–2.4) but not CEA levels. Conclusions This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.