Dept. of Pathology, Hospital Universitario Cruces, Plaza de Cruces s/n, Bizkaia, Spain.
Am J Physiol Renal Physiol. 2012 Dec 15;303(12):F1584-91. doi: 10.1152/ajprenal.00477.2012. Epub 2012 Sep 26.
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.
已有多项研究提出,蛋白酶的表达和活性可能对透明细胞肾细胞癌(CCRCC)的生存具有预测价值。针对这一问题,大多数研究都集中在分析基质金属蛋白酶(MMP)上,而对其他蛋白酶(如肽酶)的作用研究甚少。本研究采用荧光法对 79 例 CCRCC 患者的 9 种肽酶(APN、APB、ASP、CAP、DPP-IV、NEP/CD10、PEP、PGI 和 PSA)的催化活性进行了定量分析,并对生存情况(Kaplan-Meier 曲线、对数秩检验和 Cox 多因素分析)进行了分析。结果显示,膜结合型 APN 和可溶性 APN、DPP-IV 和 CAP 活性较高的 CCRCC 患者 5 年生存率明显低于活性较低的患者。相比之下,较高的可溶性 APB 活性与更长的生存时间显著相关。本研究数据表明,肽酶参与了 CCRCC 的生物学侵袭性,提示测量这些蛋白酶对评估 CCRCC 患者的预后具有一定的临床价值。