NFE2L2的mRNA表达水平降低与乳腺癌患者的不良预后相关。
Reduced mRNA expression levels of NFE2L2 are associated with poor outcome in breast cancer patients.
作者信息
Wolf Barbara, Goebel Georg, Hackl Hubert, Fiegl Heidi
机构信息
Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, 6020, Innsbruck, Austria.
出版信息
BMC Cancer. 2016 Oct 22;16(1):821. doi: 10.1186/s12885-016-2840-x.
BACKGROUND
The transcription factor nuclear factor erythroid 2-related factor 2 (NFE2L2; previously known as NRF2) is a crucial regulator of the intracellular antioxidant response. It controls the expression of genes involved in the detoxification and elimination of reactive oxidants and electrophilic agents. The role of NFE2L2 in cancer is subject of controversial discussion, as it has been reported to have both pro-and anti-tumourigenic functions. To shed some light on this paradox, we analysed the NFE2L2 mRNA expression levels in breast cancer and its association with clinicopathological features and survival.
METHODS
We retrospectively evaluated the NFE2L2 mRNA expression levels in tumour tissue of two independent breast cancer patient cohorts. In the training set we analysed data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). In the test set we measured the NFE2L2 mRNA expression levels in 176 breast tumour tissues by quantitative real-time reverse transcription PCR (qRT-PCR). Group differences were analysed using Mann-Whitney U-test, and associations between NFE2L2 mRNA expression levels and clinicopathological features were examined by means of univariate and multivariate survival analyses. Furthermore, we compared NFE2L2 mRNA expression levels between tumour and normal breast tissue samples by means of 108 paired samples from the The Cancer Genome Atlas (TCGA) dataset.
RESULTS
In the training set we identified an independent predictive value for high NFE2L2 mRNA expression levels [HR 0.8 (0.6-1.0), P = 0.041; HR 0.8 (0.6-1.0), P = 0.023] especially in the subgroup of oestrogen receptor (ER) positive tumours [HR 0.6 (0.4-0.9), P = 0.008; HR 0.6 (0.4-0.8), P = 0.001]. Similarly, we found this association also in the test set [HR 0.4 (0.2-0.9), P = 0.031] and again, more pronounced in patients with ER positive tumours [HR 0.2 (0.1-0.7), P = 0.012]. In addition, we observed generally lower NFE2L2 expression levels in tumour tissues than in normal breast tissues.
CONCLUSION
We concluded that reduced NFE2L2 mRNA expression in tumour tissues is an independent predictor of shortened survival in breast cancer patients.
背景
转录因子核因子红细胞2相关因子2（NFE2L2；以前称为NRF2）是细胞内抗氧化反应的关键调节因子。它控制参与活性氧化剂和亲电试剂解毒及清除的基因的表达。NFE2L2在癌症中的作用是一个有争议的讨论话题，因为据报道它具有促肿瘤和抗肿瘤功能。为了阐明这一矛盾，我们分析了乳腺癌中NFE2L2 mRNA表达水平及其与临床病理特征和生存率的关系。
方法
我们回顾性评估了两个独立乳腺癌患者队列肿瘤组织中的NFE2L2 mRNA表达水平。在训练集中，我们分析了来自国际乳腺癌分子分类联盟（METABRIC）的数据。在测试集中，我们通过定量实时逆转录PCR（qRT-PCR）测量了176个乳腺肿瘤组织中的NFE2L2 mRNA表达水平。使用曼-惠特尼U检验分析组间差异，并通过单变量和多变量生存分析检查NFE2L2 mRNA表达水平与临床病理特征之间的关联。此外，我们通过来自癌症基因组图谱（TCGA）数据集的108对样本比较了肿瘤组织和正常乳腺组织样本之间的NFE2L2 mRNA表达水平。
结果
在训练集中，我们确定高NFE2L2 mRNA表达水平具有独立的预测价值[风险比（HR）0.8（0.6 - 1.0），P = 0.041；HR 0.8（0.6 - 1.0），P = 0.023]，特别是在雌激素受体（ER）阳性肿瘤亚组中[HR 0.6（0.4 - 0.9），P = 0.008；HR 0.6（0.4 - 0.8），P = 0.001]。同样，我们在测试集中也发现了这种关联[HR 0.4（0.2 - 0.9），P = 0.031]，并且在ER阳性肿瘤患者中更为明显[HR 0.2（0.1 - 0.7），P = 0.012]。此外，我们观察到肿瘤组织中的NFE2L2表达水平总体上低于正常乳腺组织。
结论
我们得出结论，肿瘤组织中NFE2L2 mRNA表达降低是乳腺癌患者生存缩短的独立预测因素。
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