Phosphorylated S6K1 is a possible marker for endocrine therapy resistance in hormone receptor-positive breast cancer
Phosphorylated S6K1 is a possible marker for endocrine therapy resistance in hormone receptor-positive breast cancer
复制标题
DOI：
10.1007/s10549-010-1315-z
复制
发表时间：
2011-02-01
影响因子：
3.8
通讯作者：
Noh, Woo Chul
中科院分区：
文献类型：
--
作者：
Kim, Eun-Kyu;Kim, Hyun-Ah;Noh, Woo Chul
雌激素受体与哺乳动物雷帕霉素靶蛋白（mTOR）通路之间的串扰是内分泌治疗抗性的机制之一，已知磷酸化S6激酶1（p-S6 K1）是mTOR通路激活的标志物。作者根据激素受体（HR）状态评估了p-S6 K1的预后意义。在304例乳腺癌组织中评估了p-S6 K1的表达，并研究了其表达与患者预后之间的关系。在197例HR（+）肿瘤中，70例（35.5%）p-S6 K1阳性。大多数HR（+）肿瘤患者（97.5%）接受了辅助内分泌治疗。在HR（+）组中，p-S6 K1的表达是影响总生存期（OS）和乳腺癌特异性生存期（BCSS）的独立不良指标（风险比，2.62; 95%置信区间[CI]，1.19-5.76; P = 0.017和风险比，3.25; 95% CI，1.20-8.82; P = 0.020）。然而，在HR（-）组中，p-S6 K1表达与患者的生存无关。p-S6 K1的表达是HR（+）肿瘤患者预后不良的因素。这些结果表明，p-S6 K1表达可能是HR（+）肿瘤患者内分泌治疗抵抗的标志物。
Cross-talk between the estrogen receptor and the mammalian target of rapamycin (mTOR) pathway is one of the mechanisms of endocrine therapy resistance, and the phosphorylated S6 kinase 1(p-S6K1) is known to be a marker of the mTOR pathway activation. The authors assessed the prognostic significance of p-S6K1 according to the hormone receptor (HR) status. The expression of p-S6K1 was evaluated in 304 breast cancer tissues, and the association between its expression and patient outcomes was investigated. Among 197 cases with the HR (+) tumor, 70 (35.5%) were positive for p-S6K1. Most of the patients (97.5%) with the HR (+) tumor received adjuvant endocrine therapy. The expression of p-S6K1 was found to be an independent worse prognosticator affecting overall survival (OS) and breast cancer-specific survival (BCSS) in the HR (+) group (hazard ratio, 2.62; 95% confidence interval [CI], 1.19-5.76; P = 0.017 and hazard ratio, 3.25; 95% CI, 1.20-8.82; P = 0.020, respectively). In the HR (-) group, however, the p-S6K1 expression was not associated with patients' survival. The expression of p-S6K1 is a worse prognostic factor in patients with HR (+) tumors. These results suggest that the p-S6K1 expression might be a marker for endocrine therapy resistance in patients with HR (+) tumors.