Abstract
Matrix metalloproteinase-1 (MMP1) is a member of the matrix metalloproteinases family, and its aberrant expression is implicated in tumor invasion and metastasis. However, the relationship between MMP1 abnormal expression and clinical outcome in breast cancer patients remains to be elucidated. To address this issue, we conducted immunohistochemistry in breast cancer and adjacent normal tissues, and mined the transcriptional and survival data of MMP1 in breast cancer patients through Oncomine, Kaplan-Meier Plotter, bc-GenExMiner, COSMIC and cBioPortal databases. First, we found that both protein and mRNA levels of MMP1 expression were significantly higher in breast cancer tissues. Second, high MMP1 mRNA expression correlated with worse overall survival among grade II (HR = 1.75; p = 0.011), nodal-negative (HR = 2.00; p = 0.00028), ER-positive (HR = 1.61; p = 0.00027) and HER2-negative (HR = 3.17; p = 0.029) patients with breast cancer by using Kaplan-Meier plotter database. Third, the overexpression of MMP1 was associated with unfavorable survival results including overall survival (HR = 1.6; p = 1.6e-05), relapse free survival (HR = 1.78; p < 1e-16) and distant metastasis free survival (HR = 1.65; p = 5.3e-05) in patients with breast cancer. Taken together, the expression status of MMP1 is a significant prognostic indicator and a potential drug target for breast cancer.
Highlights
Breast cancer (BC) is one of the most common cancers and one of the major cause of cancer-related deaths worldwide [1]
According to the classification of Matrix metalloproteinase-1 (MMP1) IHC staining (Figure 1C), Positive MMP1 expression was observed to be positively related with the T stage (p = 0.001), while the expression of MMP1 was negatively associated with ER and PR status (p = 0.005 and 0.027, respectively)
There were no significant association between MMP1 expression and other clinicopathologic factors including age, tumor location, differential grade, lymph node infiltration, and HER2 and triple-negative breast cancer (TNBC) status (p = 0.377, 0.856, 0.394, 0.5, 0.861 and 0.188, respectively)
Summary
Breast cancer (BC) is one of the most common cancers and one of the major cause of cancer-related deaths worldwide [1]. BC is known to be a heterogeneous disease of distinct histological and biological subtypes with different pathological, molecular and clinical features. Current prognostic and predictive biomarkers have markedly improved treatment options for patients with BC, intratumor heterogeneity in BC still complicates the diagnosis and treatment, and influences the clinical outcome. More reliable markers are still required to further improve therapeutic strategy for individual patients. Matrix metalloproteinases (MMPs), a family of enzymes that degrade numerous kinds of extracellular matrix (ECM), were reported to play a key role in the metastatic process of cancer cells [2, 3]. A plenty of studies indicated that MMP1 is implicated in the progression and metastasis of tumor cells [4]
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