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

Anticancer Res. 2010 Oct;30(10):4127-30.

Abstract

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.

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Gene Expression
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / physiology
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Survival Rate
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Tumor Microenvironment

Substances

  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1