The association of MMP-9 enzyme activity, MMP-9 C1562T polymorphism, and MMP-2 and -9 and TIMP-1, -2, -3, and -4 gene expression in lung cancer

Genet Test Mol Biomarkers. 2009 Oct;13(5):671-8. doi: 10.1089/gtmb.2009.0053.

Abstract

Aim: To investigate the association of gene expression of MMP-2 and -9, and TIMP-1, -2, -3, and -4 and polymorphism frequencies of MMP-9 C1562T and plasma MMP-9 enzyme activity in lung cancer patients.

Methods: In this study, DNA and RNA samples were extracted from peripheral blood of 300 subjects (200 lung cancer patients and 100 controls). MMP-9 C1562T polymorphism was determined using restriction fragment length polymorphism (RFLP) method, and expression of MMP-2 and -9, TIMP-1, -2, -3, and -4 was determined using reverse transcriptase polymerase chain reaction. Plasma MMP-9 enzyme activity levels were measured using enzyme-linked immunosorbent assay.

Results and conclusion: The frequencies of C1562T genotypes were found to be CC 67%, CT 30%, and TT 3% in the control group and CC 75%, CT 24%, and TT 1% in the patient group. It was determined that CC genotype frequency increases significantly in patients according to control group. Plasma MMP-9 enzyme activity levels increased in patients with lung cancer compared to the control group. The cut-off value of MMP-9 enzyme activity was determined as 7.76 ng/mL by receiver operating characteristics curve analysis. The sensitivity, specificity, positive predictive value, and negative predictive value were 77%, 51%, 75.9%, and 52.6%, respectively. The expression of MMP-2 and TIMP-1 was found to be higher in lung cancer patients. Finally, we claim that determination of MMP-9 enzyme levels and expression of MMP-2 and -9 and TIMP-1 can be used as a marker in lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / genetics*
  • DNA Primers
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Polymorphism, Genetic*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinases / genetics*

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9