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Bladder cancer: evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera


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 ( more than 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. ( Xagena )

Ricci S et al, Oncol Lett 2015;10:2527-2532

XagenaMedicine_2015



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