Prognostic value of matrix metalloprotease-1/protease-activated receptor-1 axis in patients with prostate cancer

The aim of this study was to investigate the associations of matrix metalloprotease-1 (MMP-1) and its receptor protease-activated receptor-1 (PAR-1) coexpression with the clinicopathological characteristics and prognosis of patients with prostate cancer (PCa). Immunohistochemistry was performed to detect the expression changes of MMP-1 and PAR-1 proteins in 180 pairs of human PCa tissues and matched non-cancerous prostate tissues. Then, the associations of combined MMP-1 and PAR-1 expression with selected clinicopathological characteristics and patient prognosis were evaluated. Both MMP-1 and PAR-1 proteins were positively localized in cytoplasm of tumor cells in PCa tissues. Compared with non-cancerous prostate tissues, MMP-1 (PCa vs. Normal: 4.15 ± 1.28 vs. 2.37 ± 1.16, P < 0.001) and PAR-1 (PCa vs. Normal: 3.71 ± 1.21 vs. 1.55 ± 1.12, P < 0.001) protein expression were both significantly upregulated. More interestingly, the expression levels of MMP-1 in PCa tissues were positively correlated with those of PAR-1 significantly (Spearman correlation coefficient r = 0.88, P < 0.001). In addition, the coexpression of MMP-1 and PAR-1 (MMP-1-high/PAR-1-high) in PCa tissues was significantly associated with the higher Gleason score (P < 0.001), the presence of metastasis (P < 0.001) and the advanced pathological stage (P = 0.009). Furthermore, both univariate and multivariate analyses showed that MMP-1-high/PAR-1-high expression was an independent predictor for both unfavorable overall survival and biochemical recurrence-free survival. These findings confirmed for the first time that the upregulation of MMP-1 protein combined with the overexpression of PAR-1 protein may contribute to the malignant progression of PCa. More importantly, MMP-1/PAR-1 axis may be a negative prognostic factor for patients with PCa.