Hallajian Zeinab, Mahjoubi Frouzandeh, Nafissi Nahid
Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Breast Cancer. 2017 Jul;24(4):624-634. doi: 10.1007/s12282-016-0750-z. Epub 2017 Jan 5.
DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes.
50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009.
mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (P < 0.001). Spearman's test demonstrated a significant positive correlation among ATM, BRCA1 and RAD51 gene down expression (P < 0.0001). There was a significant association between down expression of ATM with stage (P < 0.05), necrosis (P < 0.05), perineural invasion (P < 0.05), vascular invasion (P < 0.01), malignancy (P ≤ 0.001), PR (P < 0.05) and ER status (P < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P < 0.01), auxiliary lymph node metastasis (P = 0.01), age (P = 0.001), grade (P < 0.05) and PR status (P < 0.05).
This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.
DNA双链断裂（DSB）作为一种严重损伤，可通过非同源末端连接和同源重组途径进行修复。ATM、BRCA1、RAD51基因参与同源重组途径。虽然一些研究揭示了这些基因在不同类型癌症中的个体表达变化，但试图评估这些基因表达变异在乳腺癌发病机制中的相关性的研究有限。本研究旨在确定新鲜乳腺癌组织中RAD51、ATM和BRCA1基因的表达水平及其与临床病理因素的关联。此外，本研究评估了这些基因表达水平之间的潜在相关性。
收集50例乳腺癌组织，通过实时PCR检测BRCA1、RAD51和ATM基因的表达。使用2009版REST软件分析表达变化。
与作为对照基因的β-肌动蛋白相比，这三个基因的mRNA表达均降低（P < 0.001）。Spearman检验显示ATM、BRCA1和RAD51基因下调表达之间存在显著正相关（P < 0.0001）。ATM下调表达与分期（P < 0.05）、坏死（P < 0.05）、神经周围浸润（P < 0.05）、血管浸润（P < 0.01）、恶性程度（P ≤ 0.001）、孕激素受体（PR）（P < 0.05）和雌激素受体（ER）状态（P < 0.01）之间存在显著关联。此外，BRCA1下调表达与Ki67之间存在显著关联（P ≤ 0.001）。而且，RAD51下调表达与淋巴结受累（P < 0.01）、腋窝淋巴结转移（P = 0.01）、年龄（P = 0.001）、分级（P < 0.05）和PR状态（P < 0.05）之间存在显著关联。
本研究表明乳腺癌常见功能途径中几种DSB修复基因的表达变化之间存在关联，以及这些基因的异常表达与重要临床预后因素之间存在显著关联。
