Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients

Abstract

Matrix metalloproteinases (MMPs) are a group of enzymes that mediate both physiological and pathological processes such as carcinogenesis. The role of matrix metalloproteinase-3 (MMP-3) and (MMP-7) in the pathogenesis of breast cancer (BC) has been demonstrated, suggesting that they may be considered as potential markers of this condition. The aim of this study was to assess plasma concentrations and diagnostic utility of MMP-3 and MMP-7 in 100 patients with early-stage breast cancer with Luminal A subtype or Luminal B HER-negative subtype, before and after surgical treatment, and in the following control groups: patients with a benign tumor (fibroadenoma) and healthy subjects. The concentrations of MMP-3 and MMP-7 were referenced to the levels of the widely recognized marker for BC diagnosis CA 15-3. MMP-3 and MMP-7 was measured by ELISA method and CA 15-3 by CMIA. Plasma levels of MMP-7 were significantly higher in Luminal A and Luminal B HER2-negative subtype breast cancer patients as compared to the healthy group. MMP-7 demonstrated comparable but mostly higher to CA 15-3 or MMP-3 values of diagnostic sensitivity, specificity, positive and negative predictive values and AUC (0.6888 for Luminal A subtype; 0.7612 for Luminal B HER2-negative; 0.7250 for BC total group, respectively) in the groups tested. The combined use of the tested parameters resulted in a further increase in diagnostic criteria and AUC. These results suggest the usefulness of combining MMP-7 with CA 15-3 in the diagnostics of breast cancer, especially in Luminal B HER2-negative subtypes patients, as a new candidate for tumor markers.

Keywords: breast cancer; ca 15-3; fibroadenoma; luminal a subtype; luminal b her2-negative subtype; mmp-3; mmp-7.

Figure 1

MMP-3 plasma concentrations (with marked median and interquartile range) in all tested groups: patients with BC, fibroadenoma subjects and healthy women.

Figure 2

MMP-7 plasma concentrations (with marked median and interquartile range) in all tested groups: patients with BC, fibroadenoma subjects and healthy women. Significant statistical differences have been marked on the figure.

Figure 3

CA 15-3plasma concentrations (with marked median and interquartile range) in all tested groups: patients with BC, fibroadenoma subjects and healthy women. Significant statistical differences have been marked on the figure.

Figure 4

MMP-3 plasma concentrations (with marked median and interquartile range) in patients (total group and subgroups) with BC and fibroadenoma subjects before and after surgery.

Figure 5

MMP-7 plasma concentrations (with marked median and interquartile range) in patients (total group and subgroups) with BC and fibroadenoma subjects before and after surgery. Significant statistical differences have been marked on the figure.

Figure 6

CA 15-3 plasma concentrations (with marked median and interquartile range) in patients (total group and subgroups) with BC and fibroadenoma subjects before and after surgery.

Figure 7

Significant correlations by Spearman’s method between MMP-7 and CA 15-3 in the entire study group and Luminal B HER2-negative subgroup.

Figure 8

Significant correlations by Spearman’s method between MMP-3 and MMP-7 3 in Luminal B HER2-negative subgroup.

Figure 9

Evaluation of diagnostic power based on area under the ROC curve (AUC) in BC-total group.

Figure 10

Evaluation of diagnostic power based on area under the ROC curve (AUC) in Luminal A subtype of BC.

Figure 11

Evaluation of diagnostic power based on the area under the ROC curve (AUC) in Luminal B subtype of BC.