Prognostic significance of tissue inhibitor of metalloproteinase-1 in breast cancer.
Prognostic significance of tissue inhibitor of metalloproteinase-1 in breast cancer.
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DOI：
10.1155/2012/290854
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发表时间：
2012
影响因子：
1.9
通讯作者：
Mackey JR
中科院分区：
文献类型：
--
作者：
Dechaphunkul A;Phukaoloun M;Kanjanapradit K;Graham K;Ghosh S;Santos C;Mackey JR
导论.尽管乳腺癌系统治疗取得了进展，但仍然需要新的预后和预测因素。金属蛋白酶组织抑制剂-1（TIMP-1）是基质金属蛋白酶（MMPs）的生理性抑制剂，具有促肿瘤和抗肿瘤作用。由于TIMP-1在乳腺癌中的作用存在争议，我们的目的是确定TIMP-1在乳腺癌中的预后意义。方法.采用单中心病例对照研究。通过基因表达微阵列和TIMP-1免疫组化分析了接受标准辅助治疗的早期乳腺癌患者的原发性乳腺癌。结果在优化的临界点，TIMP-1 RNA水平高的患者复发时间显著缩短，风险比（HR）为1.64（P = 0.04），但总生存期无显著差异（HR 1.29，P = 0.37）。尽管TIMP-1蛋白的胞浆过表达与早期复发无关（HR 1.0，P = 0.92），但高表达患者的总生存期有缩短的趋势（HR 1.41，P = 0.21）。结论.我们的数据表明，TIMP-1 RNA水平升高是早期复发的独立预后，并且在原发性乳腺癌中，高细胞质TIMP-1蛋白水平与短生存期有关联的趋势。
Introduction. Despite advances in breast cancer systemic treatment, new prognostic and predictive factors are still needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic significance of TIMP-1 in breast cancer. Methods. A single center-based case-control study was applied. Primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1. Results. At the optimized cut-point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.64 (P = 0.04), but without significant differences in overall survival (HR 1.29, P = 0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0, P = 0.92), there was a tendency for short overall survival in patients with high expression (HR 1.41, P = 0.21). Conclusions. Our data indicate that elevated TIMP-1 RNA levels are independently prognostic for early recurrence, and there is a tendency for association of high cytoplasmic TIMP-1 protein levels with short survival in primary breast cancer.