Ramón de Fata F, Ferruelo A, Andrés G, Gimbernat H, Sánchez-Chapado M, Angulo J C
Servicio de Urología, Hospital Universitario de Getafe, Fundación para la Investigación Biomédica, Universidad Europea de Madrid, Madrid, España.
Actas Urol Esp. 2013 Sep;37(8):480-8. doi: 10.1016/j.acuro.2013.05.004. Epub 2013 Jul 31.
The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer.
Quantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves.
There is a correlation between the determinations of MMP-2 and TIMP-2 (R=.699; P>.0001) and MMP-9 and TIMP-2 (R=.305; P=.049). Patients with bladder cancer have higher levels of MMP-9 (p<0.0001) and TIMP-2 (P=.047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P<.001). Differences were not detected between cancer and controls regarding age (P=.64) or gender (P=.64). Differences were also not detected regarding MMP-2 (P=.35) or MMP-2/TIMP-2 rate (P=.45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P=.022 and P=.038, respectively) and those of the TIMP-2 according to M category (P=.036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively.
The results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of bladder cancer, and a potential utility as clinical markers of the disease. Multicenter, prospective studies that confirm their preliminary results are necessary.
基于检测外周血循环和单核细胞中明胶酶mRNA（MMP-2和MMP-9）对膀胱癌进行诊断和分子分期已显示出有前景的结果。我们分析了相应蛋白质合成产物的测定是否有助于诊断和表征膀胱癌患者。
采用酶联免疫吸附测定（ELISA）技术对42例个体（31例不同分期的膀胱癌患者和11例健康对照）的血清MMP-2、MMP-9和TIMP-2水平进行定量测定。根据临床病理特征（年龄、性别、T分期、M分期或分级），对病例组与对照组（Mann-Whitney U检验）以及不同肿瘤组（Mann-Whitney U检验或Kruskal-Wallis检验）的测定结果进行比较。通过分析ROC曲线评估这些标志物的诊断效能。
MMP-2与TIMP-2的测定结果之间存在相关性（R = 0.699；P > 0.0001），MMP-9与TIMP-2的测定结果之间也存在相关性（R = 0.305；P = 0.049）。膀胱癌患者的MMP-9（P < 0.0001）和TIMP-2（P = 0.047）水平高于对照组。此外，癌症患者的MMP-9/TIMP-2比值也更高（P < 0.001）。在年龄（P = 0.64）或性别（P = 0.64）方面，癌症患者与对照组之间未检测到差异。在MMP-2（P = 0.35）或MMP-2/TIMP-2比值（P = 0.45）方面也未检测到差异。在癌症患者群体中，MMP-2和MMP-9的值根据T分期不同而有所差异（分别为P = 0.022和P = 0.038），TIMP-2的值根据M分期不同而有所差异（P = 0.036）。ROC曲线分析表明，MMP-9和MMP-9/TIMP-2比值均可区分癌症患者与对照组，诊断准确性相当（ABC 0.953），截断值分别为3.93 ng/mL（灵敏度90%；特异度81%）和0.053 ng/mL（灵敏度96%；特异度84%）。
所得结果表明，血清MMP-9和TIMP-2在预测膀胱癌的发生和进展方面均有应用价值，并且有可能作为该疾病的临床标志物。有必要进行多中心、前瞻性研究以证实其初步结果。
