MMP14 and DDR2 are potential molecular markers for metastatic triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive and rapidly invasive breast cancer types. TNBC's potential to metastasize is greater than other types of breast cancer, and current research aims at finding distinct molecular targets that may serve as potential targeted therapeutics. Here, we utilized TNBC tissue microarrays to determine the protein expression of seven matrix metalloproteinases (MMPs) and Discoidin domain receptor 2 (DDR2) in metastatic and non-metastatic TNBC to identify potential targets for immunotherapy. We found MMP1 expression inversely correlated with tumor grade, whereas MMP2, 3, 12, and 13 expression directly correlated with tumor grade (p < 0.05). Metastatic TNBC correlated with the expression of DDR2 (r = 0.231, p = 0.043), MMP11 (r = 0.272, p = 0.017), and MMP14 (r = 0.426, p < 0.001). Multi-marker models were tested for their potential to predict metastatic TNBC from non-metastatic TNBC. An all-marker model had a significant classification potential (odd ratio (OR) 23.44 (95%CI: 6.06-73.1), p < 0.0001), whereas a 3-marker model that included DDR2, MMP2, and MMP14 had similar significant classification (OR 19.4 (5.1-60.4), p < 0.0001). Moreover, model performance metrics were comparable for the two models. Therefore, we propose MMP14 and DDR2 as potential molecular markers for the detection of metastatic TNBC. In addition, further research on the efficacy of targeted dual immunotherapies against MMP14 and DDR2 in TNBC is warranted.