Ricci Serena, Bruzzese Dario, DI Carlo Angelina
Department of Translational Medical Science, University of Naples 'Federico II', Naples 80131, Italy.
Department of Public Health, University of Naples 'Federico II', Naples 80131, Italy.
Oncol Lett. 2015 Oct;10(4):2527-2532. doi: 10.3892/ol.2015.3558. Epub 2015 Aug 3.
The identification of biomarkers in urine or serum samples from patients with bladder cancer is urgently required for the development of non-invasive methods for the diagnosis of bladder carcinoma and to facilitate follow-up surveillance, to combat the high progression and recurrence rates of this type of cancer. The current study measured the content of matrix metalloproteinase (MMP)-2 and -9, as well as tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in the urine and sera of 41 patients with bladder cancer by ELISA. The association between levels of MMP-2 and -9 and TIMP-1 and -2, and tumor grade and stage were investigated to verify whether these molecules are involved in tumor differentiation. Statistical analysis of the data revealed that urinary TIMP-1 levels were significantly higher in the high grade group compared with those of the low grade samples (P=0.022). The results also revealed a significantly differing distribution of TIMP-1 expression between Ta and T1 stage specimens (P=0.040). The corresponding area under the curves (AUCs) were 0.72, with a sensitivity of 0.70 and specificity of 0.75. In addition, neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex levels in the sera were measured. All molecules evaluated were detected in the sera of the patients studied. In particular, tumors staged as non-muscle invasive (Ta and T1), demonstrated significantly higher NGAL levels compared with those of muscle invasive (>T1) bladder cancer (32.8 ng/ml vs. 16.2 ng/ml; P=0.029). The discriminatory ability of NGAL expression was confirmed by receiver operating characteristic curve analysis that revealed an AUC of 0.75, a sensitivity of 0.88 and a specificity of 0.67. These data indicated that urinary TIMP-1 and serum NGAL may be useful non-invasive biomarkers to provide clinical information for bladder cancer disease management. Multicenter, prospective studies are required to confirm these preliminary results.
膀胱癌患者的尿液或血清样本中生物标志物的鉴定对于开发非侵入性膀胱癌诊断方法以及促进后续监测以应对此类癌症的高进展和复发率而言迫在眉睫。本研究通过酶联免疫吸附测定法（ELISA）测量了41例膀胱癌患者尿液和血清中基质金属蛋白酶（MMP）-2和-9以及金属蛋白酶组织抑制剂（TIMP）-1和-2的含量。研究了MMP-2和-9以及TIMP-1和-2水平与肿瘤分级和分期之间的关联，以验证这些分子是否参与肿瘤分化。数据的统计分析显示，高级别组的尿TIMP-1水平显著高于低级别样本（P = 0.022）。结果还显示，Ta期和T1期标本中TIMP-1表达的分布存在显著差异（P = 0.040）。相应的曲线下面积（AUC）为0.72，灵敏度为0.70，特异性为0.75。此外，还测量了血清中中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和MMP-9/NGAL复合物的水平。在所研究患者的血清中检测到了所有评估的分子。特别是，非肌肉浸润性（Ta和T1）分期的肿瘤显示，与肌肉浸润性（>T1）膀胱癌相比，NGAL水平显著更高（32.8 ng/ml对16.2 ng/ml；P = 0.029）。通过受试者工作特征曲线分析证实了NGAL表达的鉴别能力，该分析显示AUC为0.75，灵敏度为0.88，特异性为0.67。这些数据表明，尿TIMP-1和血清NGAL可能是有用的非侵入性生物标志物，可为膀胱癌疾病管理提供临床信息。需要多中心前瞻性研究来证实这些初步结果。
