Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: a systematic review and meta-analysis

Abstract

Background Breast cancer (BC) is a leading cause of cancer-related death in females worldwide. Previous studies have demonstrated that matrix metalloproteinases (MMPs) play key roles in metastasis and are associated with survival in various cancers. The prognostic values of MMP2 and MMP9 expression in BC have been investigated, but the results remain controversial. Thus, we performed the present meta-analysis to investigate the associations between MMP2/9 expressions in tumor cells with clinicopathologic features and survival outcome in BC patients. Methods Eligible studies were searched in PubMed, Web of Science, EMBASE, CNKI and Wanfang databases. The associations of MMP2/9 overexpression in tumor cells with overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) were assessed by hazard ratio (HR) and 95% confidence interval (CI). The associations of MMP2/9 overexpression with clinicopathological features were investigated by calculating odds ratio (OR) and 95% CI. Subgroup analysis, sensitivity analysis, meta-regression, and analysis for publication bias were performed. Results A total of 41 studies comprising 6517 patients with primary BC were finally included. MMP2 overexpression was associated with an unfavorable OS (HR = 1.60, 95% CI 1.33 –1.94, P < 0.001) while MMP9 overexpression predicted a shorter OS (HR = 1.52, 95% CI 1.30 –1.77, P < 0.001). MMP2 overexpression conferred a higher risk to distant metastasis (OR = 2.69, 95% CI 1.35–5.39, P = 0.005) and MMP9 overexpression correlated with lymph node metastasis (OR = 2.90, 95% CI 1.86 – 4.53, P < 0.001). Moreover, MMP2 and MMP9 overexpression were both associated with higher clinical stage and histological grade in BC patients. MMP9 overexpression was more frequent in patients with larger tumor sizes. Conclusions Tumoral MMP2 and MMP9 are promising markers for predicting the prognosis in patients with BC.

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development

“…In this study, MMP-2 and MMP-9 staining showed no significant differences between case and control groups, while a role of MMP-2 and MMP-9 as biomarkers for the prediction of BC progression and metastasis was not supported. These findings are not usual given that the expression levels of MMP-2 and MMP-9 in BC have been described in different studies, since not only do they exhibit proteolytic activity against basal membrane proteins, which translates into tumor invasion, but also influence tumor growth, angiogenesis, and premetastatic niche formation [81][82][83][84]. It is important to highlight that uneven expression levels of several MMP have been found in BC.…”

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

“…We show that LOX mRNA is upregulated in cells on aged matrices compared to young, and when it is knocked down, E‐CAD in cells on the aged matrix is re‐localized to cell membrane. Remarkably, cytokine levels in the aged microenvironment, especially the uPA/uPAR mediators uPA, [ 59 ] uPAR, SERPINE1, [ 60 , 61 ] ANG, [ 62 ] and OPN, [ 63 , 64 ] as well as the IL1 family [ 65 , 66 ] and IL8, [ 67 ] TGF β family, [ 68 ] MMP2, [ 69 , 70 ] which largely affect cell behavior, including proliferation, migration, and differentiation, as well as cancer progression, [ 71 ] are reduced to the young matrix levels after LOX knockdown.…”

In Silico Study of Physicochemical Characteristics and Anticancer Potential of Peptides Derived from Salvia Hispanica

“…Thus, an overexpression of MMP-2 and MMP-9 in human cancers is strongly associated with metastasis and survival rates since they play key roles in the degradation of the extracellular matrices and promoting tumor invasion and metastasis (H. Li et al, 2017; Martínez-Limón et al, 2020). Additionally, a high expression of MMP-2 and MMP-9 has also been reported to in uence cancer development and progression due to their participation in cell apoptosis, proliferation, and angiogenesis (Jiang & Li, 2021).…”