Clinical implications of proteolytic activity imbalance in breast cancer diagnosis

Cancer Biomark. 2014;14(6):409-17. doi: 10.3233/CBM-140428.

Abstract

Background: Matrix metalloproteinase-9 and its tissue inhibitor TIMP-1 have been documented as putative tumor markers because of their involvement in cancer invasion and metastasis.

Objective: The aim of our study was to elucidate the diagnostic efficacy of proteolytic activity markers among traditional tumor markers (CEA and CA15.3) and clinicopathological variables.

Methods: Serum samples were withdrawn from 160 individuals (80 patients with primary breast cancer, 40 patients with benign breast lesions and 40 individuals serve as healthy controls). MMP-9 and TIMP-1 were measured by ELISA and gelatin zymography.

Results: The best cutoff points for MMP-9 and TIMP-1 were depicted by receiver operating characteristic (ROC) curve. The positivity rates and the median levels for MMP-9 and TIMP-1 showed significant difference among the three investigated groups (P< 0.0001). MMP-9 and MMP-9/TIMP-1 were inversely related to clinical stage and lymph node involvement (P< 0.0001). TIMP-1 was significantly correlated with hormonal receptor status (ER, and PgR). MMP zymography results were comparable to those from ELISA. The sensitivity and the specificity of MMP-9, TIMP-1 and MMP-9/TIMP-1 were superior to traditional tumor markers (CEA and CA15.3) especially for early stages (T1) and low grade breast cancer patients.

Conclusion: These findings indicate that investigated biomarkers are constructive for early diagnosis of breast cancer and MMP-9/TIMP-1 ratio might be a new significant marker in predicting breast cancer development.

Keywords: Breast cancer; MMP-9; TIMP-1; early diagnosis; zymography.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood*
  • Breast Neoplasms / pathology
  • Early Detection of Cancer*
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Peptide Hydrolases / blood
  • Prognosis
  • Receptors, Cell Surface / blood
  • Tissue Inhibitor of Metalloproteinase-1 / blood*

Substances

  • Biomarkers, Tumor
  • Receptors, Cell Surface
  • Tissue Inhibitor of Metalloproteinase-1
  • carcinoembryonic antigen binding protein, human
  • Peptide Hydrolases
  • Matrix Metalloproteinase 9