Abstract
Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.
Highlights
Studies of pathological processes associated with tumour growth, and the occurrence of lymph node metastases and distant metastases reveal that matrix metalloproteinases (MMPs) are key proteins involved in shaping the tumour microenvironment and impacting cancer progression and metastases [2,3]
Concentrations of all tested parameters were significantly higher in patients with stage III and IV breast cancer (BC) in comparison to benign breast tumour subjects (p < 0.001), in whom, the concentration of MMP-7 was higher than in healthy participants (p = 0.03)
Our results indicate that MMP-7 and MMP-26 are promising markers in the diagnosis of BC
Summary
Breast cancer (BC) is the most commonly diagnosed cancer in females worldwide. It most frequently originates in the lactiferous ducts as a result of uncontrolled proliferation of epithelial cells [1]. Studies of pathological processes associated with tumour growth, and the occurrence of lymph node metastases and distant metastases reveal that matrix metalloproteinases (MMPs) are key proteins involved in shaping the tumour microenvironment and impacting cancer progression and metastases [2,3]. MMPs are a family of a proteolytic enzymes responsible for remodelling of the extracellular matrix (ECM). The majority of MMPs consist of a propeptide, a catalytic metalloproteinase domain, a linker peptide of variable lengths and a hemopexin (Hpx) domain.
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