Department of Urology, University of Duisburg-Essen, Essen, Germany.
Cancer Sci. 2010 May;101(5):1300-8. doi: 10.1111/j.1349-7006.2010.01506.x. Epub 2010 Jan 20.
Matrix metalloproteinases (MMPs) play an important role in tumor progression and metastasis. Here, we investigated the prognostic relevance of MMP-7 in urinary bladder cancer. MMP-7 gene expression was measured in tissue samples of 101 patients using quantitative real-time PCR. Circulating MMP-7 serum levels of 98 individuals (79 patients and 19 controls) were analyzed by enzyme-linked immunosorbent assay. The results were compared with the clinical follow-up data, performing Kaplan-Meier log-rank test as well as univariate and multivariate Cox analysis. In representative cases, immunohistochemical analysis for MMP-7 was performed. We detected significantly elevated MMP-7 levels both in tissue and serum samples of patients with metastatic disease (P = 0.001 and P = 0.002). Multivariate analysis revealed that high MMP-7 tissue expression and serum concentration are stage- and grade-independent predictors of both metastasis-free (hazard ratio [HR] = 3.80, 95% confidence interval [CI], 1.29-11.23, P = 0.016, and HR = 2.53, 95% CI, 1.01-6.37, P = 0.048) and disease-specific survival (HR = 1.89, 95% CI, 1.00-3.55, P = 0.050 and HR = 1.95, 95% CI, 1.03-3.71, P = 0.041). Based on these findings, we conclude that MMP-7 is a promising marker to detect present and to predict future metastasis. Serum MMP-7 analysis provides information about the risk of metastasis before surgery which could help to optimize therapeutic procedures. Furthermore, high MMP-7 tissue and/or serum levels could identify patients most likely to benefit from early adjuvant chemotherapy.
基质金属蛋白酶(MMPs)在肿瘤的进展和转移中发挥着重要作用。在这里,我们研究了 MMP-7 在膀胱癌中的预后相关性。使用定量实时 PCR 测量了 101 例患者的组织样本中的 MMP-7 基因表达。通过酶联免疫吸附试验分析了 98 例个体(79 例患者和 19 例对照)的循环 MMP-7 血清水平。将结果与临床随访数据进行比较,进行 Kaplan-Meier 对数秩检验以及单变量和多变量 Cox 分析。在代表性病例中,进行了 MMP-7 的免疫组织化学分析。我们在转移性疾病患者的组织和血清样本中均检测到 MMP-7 水平显著升高(P = 0.001 和 P = 0.002)。多变量分析显示,高 MMP-7 组织表达和血清浓度是无转移(危险比 [HR] = 3.80,95%置信区间 [CI],1.29-11.23,P = 0.016 和 HR = 2.53,95% CI,1.01-6.37,P = 0.048)和疾病特异性生存(HR = 1.89,95% CI,1.00-3.55,P = 0.050 和 HR = 1.95,95% CI,1.03-3.71,P = 0.041)的独立预测因子。基于这些发现,我们得出结论,MMP-7 是一种有前途的标志物,可用于检测现有转移并预测未来转移。血清 MMP-7 分析可提供手术前转移风险的信息,这有助于优化治疗程序。此外,高 MMP-7 组织和/或血清水平可识别最有可能从早期辅助化疗中受益的患者。