The impact of peptidase activity on clear cell renal cell carcinoma survival.

Gorka Larrinaga, Lorena Blanco, Begoña Sanz, Itxaro Perez, Javier Gil, Miguel Unda, Leire Andrés, Luis Casis, José I López

Index: Am. J. Physiol. Renal Physiol. 303(12) , F1584-91, (2012)

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Abstract

Several studies have proposed that protease expression and activity may have a predictive value in the survival of clear cell renal cell carcinoma (CCRCC). Most efforts on this issue have been focused on the analysis of matrix metalloproteinases (MMP) and very little on the role of other proteases, such as peptidases. The catalytic activity of 9 peptidases (APN, APB, ASP, CAP, DPP-IV, NEP/CD10, PEP, PGI, and PSA) was quantified by fluorometric methods in a series of 79 CCRCC patients, and the results obtained were analyzed for survival (Kaplan-Meier curves, log-rank test, and Cox multivariate analysis). CCRCC patients with higher activity levels of membrane-bound APN and soluble APN, DPP-IV, and CAP had significantly shorter 5-yr survival rates than those with lower levels. By contrast, higher soluble APB activity significantly correlated with longer survival. Our data suggest the involvement of peptidases in the biological aggressiveness of CCRCC and support the usefulness of measuring these proteases to assess the prognosis of patients with CCRCC.