Overexpression of tissue inhibitor of metalloproteinase-1 gene correlates with poor outcomes in colorectal cancer.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a major endogenous regulator of matrix metalloproteinases. This study examined the relation between TIMP-1 gene expression and postoperative mortality in patients with colorectal cancer (CRC). Specimens of CRC were obtained from 202 patients. The relative expression levels of TIMP-1 mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. The expression level of the TIMP-1 gene was categorized as low or high according to the median value. The TIMP-1 level did not correlate with any clinicopathological feature. On Kaplan-Meier analysis, the 5-year overall survival rate was significantly lower in patients with high TIMP-1 (62.6%) than in those with low TIMP-1 (80.6%; p=0.0113). High TIMP-1 mRNA expression was associated with significantly poorer overall survival on univariate Cox regression analysis (p=0.013) and multivariate analysis (p=0.019). [corrected]. Overexpression of TIMP-1 thus correlated with poor outcomes in patients with CRC. Our results suggest that the TIMP-1 gene expression level might be a useful, independent prognostic factor in CRC.