ADAM-17 predicts adverse outcome in patients with breast cancer
ADAM-17 predicts adverse outcome in patients with breast cancer
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DOI：
10.1093/annonc/mdm609
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发表时间：
2008-06-01
影响因子：
50.5
通讯作者：
Duffy, M. J.
中科院分区：
文献类型：
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作者：
McGowan, P. M.;McKiernan, E.;Duffy, M. J.
ADAM-17 是一种类似基质金属蛋白酶的酶，参与释放多种配体，这些配体已被证明可以促进癌症的形成和进展。这些配体包括转化生长因子-α、双调蛋白、肝素结合表皮生长因子、表皮调节蛋白和肿瘤坏死因子-α。在这项研究中，我们通过酶联免疫吸附测定法测量了 153 例浸润性乳腺癌中总 ADAM-17 的表达。我们还通过蛋白质印迹法测量了 140 例浸润性乳腺癌的前体和活性形式。与低级别肿瘤相比，ADAM-17 的表达在高级别肿瘤中显着增加，并且与肿瘤大小、淋巴结转移和雌激素受体状态无关。 ADAM-17高表达患者的总生存期明显短于低表达患者。值得注意的是，ADAM-17 的预后影响独立于乳腺癌的传统预后因素。我们的结果进一步证明 ADAM-17 参与乳腺癌进展，从而为开发 ADAM-17 作为癌症治疗的新靶点提供了进一步的动力。
ADAM-17 is a matrix metalloproteinase-like enzyme involved in the release of several ligands that have been shown to promote both cancer formation and progression. These ligands include transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, epiregulin and tumor necrosis factor-alpha. In this investigation, we measured the expression of total ADAM-17 by enzyme-linked immunosorbent assay in 153 invasive breast cancers. We also measured the precursor and active forms by western blotting in 140 invasive breast cancers. Expression of ADAM-17 was significantly increased in high-grade compared with low-grade tumors and was independent of tumor size, lymph node metastasis and estrogen receptor status. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for breast cancer. Our results are further evidence that ADAM-17 is involved in breast cancer progression and thus provides further impetus for exploiting ADAM-17 as new target for cancer treatment.