Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer
Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2010.12.364
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发表时间：
2011-04-01
影响因子：
4.7
通讯作者：
Song, Yong-Sang
中科院分区：
文献类型：
--
作者：
No, Jae Hong;Jeon, Yong-Tark;Song, Yong-Sang
Objective.哺乳动物雷帕霉素靶蛋白（mTOR）通路的激活通过调节蛋白质翻译的效率来增强细胞存活和生长。本研究旨在探讨活化的mTOR信号分子与上皮性卵巢癌临床病理特征的关系。对103例卵巢癌患者的标本进行免疫组织化学染色，用抗p-4 EBP 1、p-mTOR和p-p70 S6 K的抗体。化疗结束后复发时间短于6个月的肿瘤被归类为化疗耐药。p-mTOR、p-4 EBP 1和p-p70 S6 K的表达率分别为47.6%、85.4%和64.1%。p-4 EBP 1过表达与晚期（p = 0.04）、组织学分级（p < 0.01）、残留肿块（p <0.01）、较短的无病生存率（p = 0.01）和化疗耐药性（p = 0.02）相关。p-p70 S6 K与残余肿块相关，具有边缘显著性（p = 0.06）。p-4 EBP 1表达与p-p70 S6 K表达相关（r = 0.42，p < 0.01），而p-mTOR表达与其下游效应因子及预后因素无关。我们的研究结果表明，p-4 EBP 1表达与卵巢癌的预后不良因素有关，p-4 EBP 1过表达可能是卵巢癌的预后生物标志物。(C)2011 Elsevier Inc. All rights reserved.
Objective. Activation of the mammalian target of rapamycin (mTOR) pathway enhances cell survival and growth by regulating the efficiency of protein translation. This study was conducted to evaluate the association of activated mTOR signaling molecules with the clinicopathologic characteristics in epithelial ovarian cancer.Methods. Immunohistochemical staining with antibodies against p-4EBP1, p-mTOR, and p-p70S6K were performed on specimens of 103 patients with ovarian cancer. Tumors were classified as chemoresistant in cases where time to recurrence after the end of chemotherapy was shorter than 6 months.Results. Expressions of p-mTOR, p-4EBP1, and p-p70S6K were detected in 47.6%, 85.4%, and 64.1% of all patients, respectively. p-4EBP1 overexpression was associated with advanced stage (p = 0.04), histologic grade (p < 0.01), residual mass (p < 0.01), shorter disease-free survival rate (p = 0.01) and chemoresistance (p = 0.02). p-p70S6K was associated with residual mass with marginal significance (p = 0.06). p-4EBP1 expression was correlated with p-p70S6K expression (r = 0.42, p < 0.01), whereas p-mTOR was not associated with expression of its downstream effectors or prognostic factors.Conclusions. Our findings suggest that p-4EBP1 expression was associated with poor prognostic factors of ovarian cancer and that p-4EBP1 overexpression may be a prognostic biomarker of ovarian cancer. (C) 2011 Elsevier Inc. All rights reserved.