Ann Lab Med.  2016 May;36(3):223-229. 10.3343/alm.2016.36.3.223.

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

• Lawicki S
• Glazewska
• Sobolewska M
• Bedkowska
• Szmitkowski M

• KMID: 2373531
• DOI: http://doi.org/10.3343/alm.2016.36.3.223

Abstract

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.

Keyword

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

MeSH Terms

Adult
Aged
Area Under Curve
Biomarkers, Tumor/*blood
Breast Neoplasms/*diagnosis/genetics/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
Macrophage Colony-Stimulating Factor
Matrix Metalloproteinase 9
Mucin-1
Tissue Inhibitor of Metalloproteinase-1

Figure

• 

  Fig. 1 Diagnostic criteria of ROC curve for tested parameters and in combination with CA 15-3 in total breast cancer group.Abbreviations: MMP-9, matrix metalloproteinase-9; TIMP-1, tissue inhibitor of metalloproteinases-1; M-CSF, macrophage colony-stimulating factor.

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