McGowan P M, Duffy M J
Department of Pathology and Laboratory Medicine, St Vincent's University Hospital, Dublin 4, Ireland.
Ann Oncol. 2008 Sep;19(9):1566-72. doi: 10.1093/annonc/mdn180. Epub 2008 May 23.
Traditionally, matrix metalloproteinases (MMPs) have been implicated in cancer invasion and metastasis. Because of their role in these processes, several MMPs have been investigated for potential prognostic value as well as targets for antimetastatic therapy. In this investigation, we used a publically available database to relate messenger RNA expression levels for 17 different MMPs to tumor characteristics and outcome in patients with breast cancer. Of the MMPs investigated, only MMP-1 was significantly increased in tumors >2 cm in size compared with those <or=2 cm while MMP-1, -9, -12 and -15 were significantly elevated in high-grade compared with low-grade tumors. Only MMP-10 was higher in lymph node-positive compared with lymph node-negative cancers. Using univariate analysis, high expressions of MMP-1, -9, -12, -14 and -15 were associated with poor overall survival. Of these five, only MMP-14 predicted outcome independent of tumor size, tumor grade and lymph node status. None of the MMPs investigated were associated with good outcome. We conclude that only a minority of MMPs, i.e. MMP-1, -9, -12, -14 and -15, are associated with adverse outcome in patients with breast cancer. These MMPs are likely to be involved in mediating breast cancer progression and may thus be good targets for designing specific MMP inhibitors for the treatment of breast cancer.
传统上,基质金属蛋白酶(MMPs)被认为与癌症侵袭和转移有关。由于它们在这些过程中的作用,几种MMPs已被研究其潜在的预后价值以及作为抗转移治疗的靶点。在本研究中,我们使用一个公开可用的数据库,将17种不同MMPs的信使核糖核酸表达水平与乳腺癌患者的肿瘤特征和预后相关联。在所研究的MMPs中,与大小≤2 cm的肿瘤相比,只有MMP-1在大小>2 cm的肿瘤中显著增加,而与低级别肿瘤相比,MMP-1、-9、-12和-15在高级别肿瘤中显著升高。与淋巴结阴性癌症相比,只有MMP-10在淋巴结阳性癌症中更高。使用单变量分析,MMP-1、-9、-12、-14和-15的高表达与总体生存率差相关。在这五种中,只有MMP-14能独立于肿瘤大小、肿瘤分级和淋巴结状态预测预后。所研究的MMPs均与良好预后无关。我们得出结论,只有少数MMPs,即MMP-1、-9、-12、-14和-15,与乳腺癌患者的不良预后相关。这些MMPs可能参与介导乳腺癌进展,因此可能是设计用于治疗乳腺癌的特异性MMP抑制剂的良好靶点。