Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer

Ann Lab Med. 2016 May;36(3):223-9. doi: 10.3343/alm.2016.36.3.223.


Background: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups.

Methods: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA).

Results: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653).

Conclusions: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

Keywords: Breast cancer; CA 15-3; M-CSF; MMP-9; TIMP-1.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Female
  • Humans
  • Macrophage Colony-Stimulating Factor / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Mucin-1 / blood
  • Neoplasm Staging
  • Poland
  • ROC Curve
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-1 / blood*


  • Biomarkers, Tumor
  • Mucin-1
  • Tissue Inhibitor of Metalloproteinase-1
  • Macrophage Colony-Stimulating Factor
  • Matrix Metalloproteinase 9