Kotzsch Matthias, Farthmann Juliane, Meye Axel, Fuessel Susanne, Baretton Gustavo, Tjan-Heijnen Vivianne C G, Schmitt Manfred, Luther Thomas, Sweep Fred C G J, Magdolen Viktor, Span Paul N
Institute of Pathology, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
Eur J Cancer. 2005 Nov;41(17):2760-8. doi: 10.1016/j.ejca.2005.09.002. Epub 2005 Oct 26.
Recently, two components of important protease systems in cancer, i.e., the urokinase plasminogen activator receptor (uPAR) mRNA splice variant uPAR-del4/5 and the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), were independently reported to be of prognostic value in breast cancer. In the present study, we have evaluated the impact of both these factors on disease-free survival (DFS) in 205 breast cancer patients by assessing mRNA expression in tumour tissue by quantitative PCR. High uPAR-del4/5 mRNA expression was associated with shorter DFS in breast cancer patients (P=0.0363), whereas high TIMP-3 mRNA levels were associated with a good prognosis (P=0.0049). Furthermore, by combining uPAR-del4/5 with TIMP-3 values, we demonstrate that breast cancer patients with high uPAR-del4/5 and low TIMP-3 mRNA levels had a highly significantly shorter DFS in comparison to those patients with low uPAR-del4/5 and high TIMP-3 mRNA expression (P<0.0001). These patients had a more than 6-fold higher risk for disease recurrence or death in multivariate analysis. Therefore, considering the prognostic impact of two proteolytic factors stemming from complementary protease systems may improve the prediction of disease recurrence in breast cancer.
最近，癌症中重要蛋白酶系统的两个组成部分，即尿激酶型纤溶酶原激活物受体（uPAR）mRNA剪接变体uPAR-del4/5和基质金属蛋白酶-3组织抑制剂（TIMP-3），被分别报道在乳腺癌中具有预后价值。在本研究中，我们通过定量PCR评估肿瘤组织中的mRNA表达，来评价这两个因素对205例乳腺癌患者无病生存期（DFS）的影响。uPAR-del4/5 mRNA高表达与乳腺癌患者较短的DFS相关（P = 0.0363），而TIMP-3 mRNA高水平与良好的预后相关（P = 0.0049）。此外，通过将uPAR-del4/5与TIMP-3值相结合，我们证明，与uPAR-del4/5低表达和TIMP-3 mRNA高表达患者相比，uPAR-del4/5高表达和TIMP-3 mRNA低水平的乳腺癌患者DFS显著缩短（P < 0.0001）。在多变量分析中，这些患者疾病复发或死亡的风险高出6倍多。因此，考虑来自互补蛋白酶系统的两种蛋白水解因子的预后影响，可能会改善乳腺癌疾病复发的预测。
