Wang Jian, Liu Dingyi, Zhou Wenlong, Wang Mingwei, Xia Weimu, Tang Qi
Department of Urology, Punan Hospital of Shanghai, Pudong New District, Shanghai, 200125, China.
Med Oncol. 2014 Jun;31(6):968. doi: 10.1007/s12032-014-0968-6. Epub 2014 May 8.
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.
本研究旨在探讨基质金属蛋白酶-1（MMP-1）及其受体蛋白酶激活受体-1（PAR-1）共表达与前列腺癌（PCa）患者临床病理特征及预后的关系。采用免疫组织化学方法检测180对人PCa组织及配对的癌旁前列腺组织中MMP-1和PAR-1蛋白的表达变化。然后，评估MMP-1和PAR-1联合表达与所选临床病理特征及患者预后的关系。MMP-1和PAR-1蛋白均在PCa组织肿瘤细胞的细胞质中呈阳性定位。与癌旁前列腺组织相比，MMP-1（PCa组 vs. 正常组：4.15±1.28 vs. 2.37±1.16，P<0.001）和PAR-1（PCa组 vs. 正常组：3.71±1.21 vs. 1.55±1.12，P<0.001）蛋白表达均显著上调。更有趣的是，PCa组织中MMP-1的表达水平与PAR-1的表达水平显著正相关（Spearman相关系数r = 0.88，P<0.001）。此外，PCa组织中MMP-1和PAR-1的共表达（MMP-1高/PAR-1高）与更高的Gleason评分（P<0.001）、转移的存在（P<0.001）和晚期病理分期（P = 0.009）显著相关。此外，单因素和多因素分析均显示，MMP-1高/PAR-1高表达是不良总生存和无生化复发生存的独立预测因素。这些发现首次证实，MMP-1蛋白上调与PAR-1蛋白过表达相结合可能促进PCa的恶性进展。更重要的是，MMP-1/PAR-1轴可能是PCa患者的不良预后因素。
