Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer
Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer
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DOI：
10.1002/ijc.23337
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发表时间：
2008-05-01
影响因子：
6.4
通讯作者：
Xu, Xiao-Chun
中科院分区：
文献类型：
--
作者：
Wu, Zheng-Sheng;Wu, Qiang;Xu, Xiao-Chun
肿瘤进展和转移是乳腺癌死亡的主要原因。基质金属蛋白酶（MMPs）和金属蛋白酶的组织抑制剂（TIMPs）被认为参与肿瘤的进展和转移。因此，我们确定乳腺癌患者中MMP-9和TIMP-1的表达是否与预后相关。采用酶联免疫吸附法测定60例乳腺癌患者、18例乳腺良性疾病患者和15例健康对照者血清MMP-9和TIMP-1水平。通过免疫组织化学和原位杂交技术，对60例乳腺癌石蜡包埋肿瘤组织中MMP-9和TIMP-1蛋白及mRNA的表达进行了检测。然后，我们将乳腺癌样本中血清和组织中MMP-9和TIMP-1的水平及其表达与患者的临床病理特征联系起来。我们发现乳腺癌患者血清中MMP-9和TIMP-1的水平明显高于良性乳腺疾病和健康对照。血清中高水平的MMP-9和TIMP-1与淋巴结转移、较高的肿瘤分期、较低的无复发生存率和总生存率（OS）相关。与低表达相比，MMP-9蛋白在组织中的高表达与淋巴结转移和肿瘤分期升高有关；TIMP-1的高组织表达与较低的OS率相关。我们的研究结果表明，MMP-9和TIMP-1可能进一步被评估为预测乳腺癌进展和预后的生物标志物。(C) 2008 Wiley-Liss, Inc。
Tumor progression and metastasis contribute to the great majority of breast cancer deaths. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression and metastasis. Thus, we determined whether the expression of MMP-9 and TIMP-1 is associated with prognosis in breast cancer patients. We measured serum MMP-9 and TIMP-1 by enzyme-linked immunosorbent assay in 60 breast cancer patients, 18 benign breast disease patients and 15 healthy controls. We also evaluated the expression of MMP-9 and TIMP-1 protein and mRNA in paraffin-embedded tumor tissues from the 60 breast cancer patients by immunohistochemistry and in situ hybridization. We then correlated serum and tissue levels of MMP-9 and TIMP-1 in breast cancer samples and their expression with patients' clinicopathologic characteristics. We found that serum levels of MMP-9 and TIMP-1 were significantly higher in breast cancer patients than in benign breast disease and in healthy controls. High serum levels of MMP-9 and TIMP-1 were associated with lymph node metastasis, higher tumor stage and lower relapse-free and overall survival (OS) rates. Compared to low expression, high tissue expression of MMP-9 protein was associated with lymph node metastasis and higher tumor stage; and high tissue expression of TIMP-1 was associated with a lower OS rate. Our findings suggest that MMP-9 and TIMP-1 may further be evaluated as biomarkers for predicting progression and prognosis of breast cancer. (C) 2008 Wiley-Liss, Inc.