Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer

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.

The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes to Hepatocellular Carcinoma Susceptibility

“…These extracellular matrix components have been reported to be produced by gastrointestinal, prostatic, endometrial and breast tumor cells (63). In the literature, MMP-7 is expressed by several types of cancer cells, including esophagus, stomach (64), pancreas (65,66), lung (67), breast (68), prostate, endometrium (69), head and neck (70), and most noticeable liver (68,71). Therefore, MMP-7 is supposed to serve as a practical marker and a potential therapeutic intervention target (65,66,69,71,72).…”

Risk Association of TOX3 and MMP7 Gene Polymorphisms with Sporadic Breast Cancer in Mexican Women

“…MMPs have a relevant function in the epithelial-mesenchymal transition, by degrading proteolytically the extracellular matrix [ 22 , 42 ]. It is essential to identify the biological mechanism by which MMP SNPs confer risk against BC.…”

Molecular characterization of matrix metalloproteinase gene family across primates

“…In this article, we report positive selection for MMP-26, and evident sequence divergence for MMP-3, MMP-11, MMP-15 and MMP-17. MMP-26 has been indicated to associate with a wide range of pathological process, such as breast cancer, glioma, wounds and ischemic stroke, but lack of evidence highlights necessity of further investigation of this gene [ 49 – 52 ]. We also showed decline of expression for MMP-11 in testis and the same trend for MMP-15 in ovary during human aging.…”