Estrogen receptor-related genes as an important panel of predictors for breast cancer response to neoadjuvant chemotherapy

Estrogen receptor-related genes as an important panel of predictors for breast cancer response to neoadjuvant chemotherapy
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雌激素受体相关基因是乳腺癌对新辅助化疗反应的重要预测因子。

DOI:
10.1016/j.canlet.2010.12.014
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发表时间:
2011-03-01
期刊:
影响因子:
9.7
通讯作者:
Wu, Jiong
Wu, Jiong
中科院分区:
医学1区
文献类型:
--
作者:
Chen, Yizuo;Chen, Canming;Wu, Jiong

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目的:临床数据表明雌激素受体 (ER) 有助于化疗反应。然而,仅凭 ER 状态并不能始终如一地进行预测。在这项研究中,我们使用微阵列方法来寻找新的预测化疗反应的ER相关基因,希望提供一种稳健的多变量预测方法。方法:纳入了110名II期和III期乳腺癌患者。他们接受了四个术前周期的每周一次的 PCb(紫杉醇加卡铂)治疗方案。总共 55 个训练案例用于标记物发现和鉴定可能与化疗反应相关的任何 ER 相关基因(“训练案例”)。其他 55 名患者可作为独立验证集(“验证案例”)使用免疫组织化学 (IHC) 进行测试。结果:在训练集中,鉴定出 20 个显着差异表达的基因。在这20个基因中,TFF1、ESR1、GATA3和TFF3被发现与ER相关。在55个独立验证病例中,单变量分析表明临床变量和ER相关基因均与pCR显着相关。结果表明,当这五个因素均为阴性时,pCR率高达80%。相比之下,这五个因素在 9 名化疗耐药患者中的 7 名均呈阳性。结论:结合 ER 相关基因的水平,ER 蛋白的表达可能为新辅助化疗的反应提供重要的预测结果,并可能允许识别可以从化疗中显着受益(或可能对化疗产生耐药性)的患者亚组。 (C) 2010 Elsevier Ireland Ltd. 保留所有权利。
Purpose: Clinical data suggest that the estrogen receptor (ER) contributes to chemotherapeutic responsiveness. However, ER status alone is not consistently predictive. In this study, we used a microarray approach to find novel ER-related genes that predicted chemotherapy responses, with the hope of providing a robust multi-variable prediction method.Methods: One hundred and ten patients with stages II and III breast cancer were included. They received four preoperative cycles of a weekly PCb (paclitaxel plus carboplatin) regimen. A total of 55 training cases were used for marker discovery and for identification of any ER-related genes that may have been associated with a chemotherapeutic response ("training cases"). The other 55 patients were available as an independent validation set ("validation cases") to test, using immunohistochemistry (IHC).Results: In the training set, 20 significantly differentially expressed genes were identified. Among these 20 genes, TFF1, ESR1, GATA3 and TFF3 were found to be ER-related. Among 55 independent validation cases, univariate analysis indicated that clinical variables and ER-related genes were all significantly associated with pCR. It was shown that the pCR rate was as high as 80% when these five factors were all negative. In contrast, these five factors were all positive in seven of nine chemo-resistant patients.Conclusion: In conjunction with levels of ER-related genes, expression of ER protein may provide important predictive outcomes for responses to neoadjuvant chemotherapy and may allow for the identification of a subgroup of patients who could significantly benefit from chemotherapy (or who may be resistant to it). (C) 2010 Elsevier Ireland Ltd. All rights reserved.