Increased expression of miR-126 and miR-10a predict prolonged relapse-free time of primary oestrogen receptor-positive breast cancer following tamoxifen treatment
Increased expression of miR-126 and miR-10a predict prolonged relapse-free time of primary oestrogen receptor-positive breast cancer following tamoxifen treatment
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DOI：
10.1016/j.ejca.2013.07.145
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发表时间：
2013-11-01
影响因子：
8.4
通讯作者：
Brauch, Hiltrud
中科院分区：
文献类型：
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作者：
Hoppe, Reiner;Achinger-Kawecka, Joanna;Brauch, Hiltrud
背景：对于雌激素受体(ER)阳性的乳腺癌患者，他莫昔芬是一种有效的治疗选择。然而，多达40%的患者会经历远处或局部复发或死亡。MicroRNAs被认为是乳腺癌的重要预后指标。本研究旨在确定具有预测他莫昔芬疗效的microRNA。患者和方法：我们对6对匹配的接受他莫昔芬治疗的绝经后ER阳性乳腺癌患者的原发肿瘤进行了全球microRNA筛查(1105个人类microRNA)，这些患者要么没有复发，要么已经复发(中位数随访：8.84年；范围：1.28-12.7年)。该发现组的患者和验证组的81例患者(中位数随访：8.64年；范围：0.21-19.85年)于1986年至2005年在德国斯图加特的Robert Bosch医院接受治疗。结果：在前20名中，miR-126(危险比(HR)=0.56，95%可信区间(CI)：0.38-0.83；Holm-adj；P=0.022)和MIR-10a(HR=0.53，95%CI：0.33-0.85；在81名绝经后ER阳性患者的独立验证集中，经多变量COX回归分析，他莫昔芬预后的显著预测因素为：P=0.031)。基于受试者操作特征曲线所确定的截断值的Kaplan-Meier生存分析证实，miR-126和miR-10a在肿瘤中的高表达与较长的无复发时间相关(对数等级分别为P=0.037，P<；0.0001)。结论：我们的数据表明miR-126和miR-10a是接受三苯氧胺辅助治疗的早期绝经后乳腺癌患者肿瘤复发的独立预测因素。(C)2013爱思唯尔有限公司。保留所有权利。
Background: Adjuvant tamoxifen is a valid treatment option for women with oestrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response.Patients and methods: We performed a global microRNA screen (1105 human microRNAs) in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence (median follow up: 8.84 years; range: 1.28-12.7 years). Patients of this discovery set and the 81 patients of the validation set (median follow up: 8.64 years; range: 0.21-19.85 years) were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005.Results: Out of the top 20 deregulated microRNAs (12 up-regulated, eight down-regulated) miR-126 (Hazard Ratio (HR) = 0.56, 95% confidence interval (CI): 0.38-0.83; Holm-adj. P = 0.022) and miR-10a (HR = 0.53, 95% CI: 0.33-0.85; Holm-adj. P = 0.031) were identified as significant predictors of tamoxifen outcome by multivariate Cox regression analysis in the independent validation set of 81 postmenopausal, ER-positive patients. Kaplan-Meier survival analyses based on cut-offs determined by receiver operating characteristics curves confirmed that a higher expression of miR-126 and miR-10a in the patients tumour was associated with longer relapse-free time (log-rank P = 0.037, P < 0.0001, respectively).Conclusions: Our data suggest that miR-126 and miR-10a are independent predictors for tumour relapse in early postmenopausal breast cancer patients treated with adjuvant tamoxifen. (C) 2013 Elsevier Ltd. All rights reserved.