title: Evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera from patients with bladder cancer.
abstract: 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.
authors.affiliation: Department of Translational Medical Science, University of Naples 'Federico II', Naples 80131, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ricci
authors.affiliation: Department of Public Health, University of Naples 'Federico II', Naples 80131, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Bruzzese
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, 'Sapienza' University of Rome, Latina 04100, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: DI Carlo
keywords: bladder carcinoma; matrix metalloproteinase-2; matrix metalloproteinase-9; neutrophil gelatinase-associated lipocalin; sera; tissue inhibitor of metalloproteinase-1; tissue inhibitor of metalloproteinase-2; urine