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BRCA1 复合物成员 BRE 的表达可预测乳腺癌无病生存。

Expression of the BRCA1 complex member BRE predicts disease free survival in breast cancer.

机构信息

Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.

出版信息

Breast Cancer Res Treat. 2012 Aug;135(1):125-33. doi: 10.1007/s10549-012-2122-5. Epub 2012 Jun 16.

Abstract

Breast cancer is one of the leading causes of cancer mortality in women. Recent advances in gene expression profiling have indicated that breast cancer is a heterogeneous disease and the current prognostication using clinico-pathological features is not sufficient to fully predict therapy response and disease outcome. In this retrospective study, we show that expression levels of BRE, which encodes a member of the BRCA1 DNA damage repair complex, predicted disease-free survival (DFS) in non-familial breast cancer patients. The predictive value of BRE expression depended on whether patients received radiotherapy as a part of their primary treatment. In radiotherapy-treated patients, high BRE expression predicted a favorable DFS (hazard ratio (HR) = 0.47, 95 % confidence interval (CI) = 0.28-0.78, p = 0.004), while in non-treated patients, high BRE expression predicted an adverse prognosis (HR = 2.59, 95 % CI = 1.00-6.75, p = 0.05). Among radiotherapy-treated patients, the prognostic impact of BRE expression was confined to patients with smaller tumors (HR = 0.23, 95 % CI = 0.068-0.75, p = 0.015) and it remained an independent factor after correction for the other prognostic factors age, tumor size, lymph node involvement, and histological grade (HR = 0.50, CI = 0.27-0.90, p = 0.021). In addition, high BRE expression predicted a favorable relapse-free survival in a publicly available dataset of 2,324 breast cancer patients (HR = 0.59, CI = 0.51-0.68, p < 0.001). These data indicate that BRE is an interesting candidate for future functional studies aimed at developing targeted therapies.

摘要

乳腺癌是导致女性癌症死亡的主要原因之一。基因表达谱分析的最新进展表明,乳腺癌是一种异质性疾病,目前使用临床病理特征进行预后预测不足以完全预测治疗反应和疾病结局。在这项回顾性研究中,我们表明,编码 BRCA1 DNA 损伤修复复合物成员的 BRE 的表达水平可预测非家族性乳腺癌患者的无病生存(DFS)。BRE 表达的预测价值取决于患者是否接受放疗作为其主要治疗的一部分。在接受放疗的患者中,高 BRE 表达预示着良好的 DFS(风险比(HR)= 0.47,95%置信区间(CI)= 0.28-0.78,p = 0.004),而在未接受治疗的患者中,高 BRE 表达预示着不良预后(HR = 2.59,95% CI = 1.00-6.75,p = 0.05)。在接受放疗的患者中,BRE 表达的预后影响仅限于肿瘤较小的患者(HR = 0.23,95% CI = 0.068-0.75,p = 0.015),并且在纠正其他预后因素(年龄、肿瘤大小、淋巴结浸润和组织学分级)后,它仍然是一个独立的因素(HR = 0.50,CI = 0.27-0.90,p = 0.021)。此外,高 BRE 表达预测了 2324 名乳腺癌患者的公开数据集的无复发生存(HR = 0.59,CI = 0.51-0.68,p < 0.001)。这些数据表明,BRE 是未来旨在开发靶向治疗的功能研究的一个有趣候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7702/3413819/7bcd8cefcabf/10549_2012_2122_Fig1_HTML.jpg

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