Serum MMP-8 and TIMP-1 predict prognosis in colorectal cancer.
Serum MMP-8 and TIMP-1 predict prognosis in colorectal cancer.
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DOI：
10.1186/s12885-018-4589-x
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发表时间：
2018-06-22
期刊：
影响因子：
3.8
通讯作者：
Haglund C
中科院分区：
文献类型：
--
作者：
Böckelman C;Beilmann-Lehtonen I;Kaprio T;Koskensalo S;Tervahartiala T;Mustonen H;Stenman UH;Sorsa T;Haglund C
几乎所有的细胞外基质（ECM）成分都可以被内蛋白酶-基质金属蛋白酶（MMP）降解。MMPs的重要调节剂，从而细胞外环境的重要调节剂，是金属蛋白酶的组织抑制剂（TIMP），特别是TIMP-1。早期肿瘤发展以及远处转移可能是MMP/TIMP比例失衡改变ECM的结果。MMPs在几种炎症性疾病中升高。我们的目的是研究MMP-8，-9和TIMP-1在结直肠癌（CRC）中的预后作用及其与炎症的关系。我们纳入了1998-2011年在芬兰赫尔辛基大学医院接受手术的337名结直肠癌患者和47名对照。血清MMP-8和血浆C-反应蛋白（CRP）水平测定与时间分辨免疫荧光法（IFMA），MMP-9和TIMP-1与商业酶联免疫吸附测定（ELISA）试剂盒。采用Mann-Whitney U、Kruskal-Wallis和斯皮尔曼秩相关检验进行关联和相关性分析。根据Kaplan-Meier方法构建生存曲线，并与对数秩检验进行比较。在晚期疾病患者中，血清MMP-8和TIMP-1水平升高。MMP-8高表达（HR 1.72，95%CI 1.17-2.52，P = 0.005）和TIMP-1高表达（HR 1.80，95%CI 1.23-2.64，P = 0.002）的CRC患者的预后较差。MMP-9水平不能作为预后因素。多因素生存分析显示，Dukes分期、MMP-9/TIMP-1摩尔比低（HR 0.46，95% CI 0.33-0.98，P = 0.042）是预后的独立预测因素。CRP与MMP-8（rS = 0.229，P < 0.001）和TIMP-1（rS = 0.280，P < 0.001）呈弱相关。在无全身炎症反应的患者中，MMP-8（HR 1.66，95% CI 1.10-2.53，P = 0.017）和TIMP-1（HR 1.59，95% CI 1.05-2.42，P = 0.029）是预后因素。血清MMP-8和TIMP-1水平与结直肠癌患者的预后有关，而MMP-9水平与结直肠癌患者的预后无关。在无全身炎症反应的患者中，MMP-8和TIMP-1可能与不良预后相关。本文的在线版本（10.1186/s12885-018-4589-x）包含补充材料，可供授权用户使用。
Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, − 9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation. We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998–2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test. Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17–2.52, P = 0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23–2.64, P = 0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33–0.98, P = 0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS = 0.229, P < 0.001), and TIMP-1 (rS = 0.280, P < 0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10–2.53, P = 0.017) and TIMP-1 (HR 1.59, 95% CI 1.05–2.42, P = 0.029) were prognostic factors. MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis. The online version of this article (10.1186/s12885-018-4589-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Biasi F;Guina T;Maina M;Nano M;Falcone A;Aroasio E;Saracco GM;Papotti M;Leonarduzzi G;Poli G
通讯作者：
Poli G
影响因子：
28.4
作者：
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影响因子：
6.8
作者：
Chang, Pi-Yueh;Kuo, Yung-Bin;Chan, Err-Cheng
通讯作者：
Chan, Err-Cheng
影响因子：
14.5
作者：
Bourboulia D;Stetler-Stevenson WG
通讯作者：
Stetler-Stevenson WG
基质金属蛋白酶及其在结直肠癌中的抑制剂的行为。
影响因子：
5.6
作者：
Herszényi L;Hritz I;Lakatos G;Varga MZ;Tulassay Z
通讯作者：
Tulassay Z