Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib
Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib
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DOI：
10.1016/j.urolonc.2014.01.016
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发表时间：
2014-07-01
影响因子：
2.7
通讯作者：
Fujisawa, Masato
中科院分区：
文献类型：
--
作者：
Miyake, Hideaki;Nishikawa, Masatomo;Fujisawa, Masato
目的：评估循环基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）在接受舒尼替尼治疗的转移性肾癌（mRCC）患者中作为疾病进展预测因子的意义。材料和方法：在基线和每个治疗周期的第一天，使用酶联免疫吸附法测定52例接受舒尼替尼治疗的mRCC患者血清中MMP-2、MMP-9、TEMP-1和TIMP-2的循环水平，直到进展。结果：舒尼替尼无反应组MMP-9基线水平显著高于反应组，而无反应组TIMP-2基线水平显著低于反应组。然而，在反应者和无反应者之间，血清MMP-2和TIMP-1水平无显著差异。无应答者基线时血清MMP-9/TEMP-2比值也显著高于应答者。单因素分析显示，MMP-9/TIMP-2比值与无进展生存期显著相关，而MMP-9和TEMP-2水平与无进展生存期无显著相关；多因素分析显示，MMP-9/TIMP-2比值、Memorial Sloan-Kettering Cancer Center分级和c反应蛋白水平与无进展生存期独立相关。此外，尽管血清MMP-9和TIMP-2水平在基线和进展时间之间没有显著差异，但进展时的MMP-9/TIMP-2比值与基线比值相比显着升高。结论：血清MMP-9和TIMP-2水平的不平衡可能是预测舒尼替尼治疗的mRCC患者疾病进展的一种新的生物标志物。(C) 2014爱思唯尔公司版权所有。
Objectives: To assess the significance of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as predictors of disease progression in patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib.Materials and methods: Circulating levels of MMP-2, MMP-9, TEMP-1, and TIMP-2 in sera from 52 patients with mRCC treated with sunitinib were measured at the baseline and on the first day of each treatment cycle until progression using enzyme-linked immunosorbent assays.Results: The baseline level of MMP-9 in nonresponders to sunitinib was significantly higher than that in responders, whereas the baseline level of TIMP-2 in nonresponders was significantly lower than that in responders. However, there were no significant differences in the serum levels of MMP-2 and TIMP-1 between responders and nonresponders. The serum MMP-9/TEMP-2 ratio at the baseline in nonresponders was also significantly higher than that in responders. Univariate analysis showed that the MMP-9/TIMP-2 ratio, but not MMP-9 and TEMP-2 levels, was significantly correlated with progression-free survival, and the MMP-9/TIMP-2 ratio, in addition to the Memorial Sloan-Kettering Cancer Center classification and C-reactive protein level, appeared to be independently associated with progression-free survival on multivariate analysis. Furthermore, despite the lack of significant differences in the serum levels of MMP-9 and TIMP-2 between the baseline and the time of progression, the MMP-9/TIMP-2 ratio at the time of progression was significantly elevated compared with the baseline ratio.Conclusions: An imbalance between the serum MMP-9 and TIMP-2 levels could be a novel biomarker to predict disease progression in patients with mRCC under treatment with sunitinib. (C) 2014 Elsevier Inc. All rights reserved.