Hypoxia-inducible factor-1α correlates with MET and metastasis in node-negative breast cancer
Hypoxia-inducible factor-1α correlates with MET and metastasis in node-negative breast cancer
复制标题
DOI：
10.1007/s10549-006-9360-3
复制
发表时间：
2007-06-01
影响因子：
3.8
通讯作者：
Lee, Wen-Ying
中科院分区：
文献类型：
--
作者：
Chen, Helen H. W.;Su, Wu-Chou;Lee, Wen-Ying
肿瘤缺氧促进转移的机制尚不清楚。低氧诱导因子-1α(HIF-1α)是细胞对低氧反应的关键介质，并与MET启动子结合，导致MET表达增加。在乳腺癌中，MET的过度表达与转移性疾病导致的死亡有关。本研究的目的是探讨HIF-1α在淋巴转移阴性乳腺癌MET表达和转移中的作用。我们招募了104名接受过初次手术的T1-2N0M0乳腺癌患者作为研究对象。53名患者有远处转移，51名患者10年以上没有任何疾病证据。用免疫组织化学方法分析HIF-1α和MET在这些患者中的表达。HIF-1α和MET呈正相关(Spearman等级相关系数0.35；P<；0.01)，是远处转移的独立预测因素(P=0.002和P=0.03)，并与较差的10年无瘤生存率相关(P<；0.001)。此外，HIF-1α和MET的共同过度表达是远处转移的显著独立预测因子(奇数比，10.78；P<；0.001)，并且共同过度表达的患者的10年无瘤生存率明显较差。这些结果为HIF-1α诱导MET过度表达促进肿瘤转移提供了证据，并强调了HIF-1α作为抗转移靶点在无淋巴结转移乳腺癌中的应用前景。
The mechanism of tumor hypoxia promoting metastasis remains uncertain. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key mediator of the cellular response to hypoxia and binds the met promoter, resulting in increased expression of MET. In breast cancer, MET overexpression is associated with death caused by metastatic disease. Aim of this study is to investigate the role of HIF-1 alpha in MET expression and metastasis in lymph node negative breast cancer. We recruited a homogeneous cohort of 104 patients with T1-2N0M0 breast carcinoma, who had undergone primary surgery. Fifty-three patients had distant metastases and 51 patients had no evidence of disease for more than 10 years. We analyzed the expressions of HIF-1 alpha and MET in these patients using immunohistochemistry. HIF-1 alpha and MET were positively correlated (Spearman's rank correlation coefficient, 0.35; P < 0.01), were independent predictors of distant metastasis (P = 0.002 and P = 0.03, respectively), and correlated with poor 10-year disease-free survival rate (P < 0.001 for both). Furthermore, co-overexpression of HIF-1 alpha and MET was a significant independent predictor of distant metastasis (odd radio, 10.78; P < 0.001), and patients with co-overexpression had a significantly worse 10-year disease-free survival rate. The results provide evidence that tumor hypoxia promotes metastasis through the induction of MET overexpression by HIF-1 alpha and emphasize the promising status of HIF-1 alpha as a therapeutic target against metastasis in node-negative breast cancer.