Serum tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) levels in colorectal cancer patients: associations with clinicopathological variables and patient survival

Abstract

Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. The aim of the present study was to elucidate the diagnostic and prognostic utility of TIMP-1 and TIMP-2 in patients with colon cancer. Serum TIMP-1 and TIMP-2 concentrations were quantified using an enzyme-linked immunosorbent assay in 97 colon cancer patients. Elevated serum TIMP-1 levels were found in patients with advanced disease stage (p=0.0512) and poorly differentiated histopathological tumor grade (p=0.0059). Patients with increased TIMP-1 levels had shorter overall survival times (log-rank test, p=0.0143). Multivariate analysis also identified TIMP-1 as an independent prognostic factor (Cox regression analysis, p=0.0149). Serum TIMP-2 levels were not significantly associated with disease stage, histopathological grade or survival. In the subgroup of patients with well and moderately differentiated tumors, TIMP-1 and TIMP-2 were identified as independent prognostic factors (Cox regression analysis, p=0.0379 and p=0.0451, respectively). In conclusion, assessment of serum TIMP-1 can be considered a useful biomarker in colon cancer, whereas TIMP-2 appears to be of limited value.