Vuaroqueaux Vincent, Urban Patrick, Labuhn Martin, Delorenzi Mauro, Wirapati Pratyaksha, Benz Christopher C, Flury Renata, Dieterich Holger, Spyratos Frédérique, Eppenberger Urs, Eppenberger-Castori Serenella
Stiftung Tumorbank Basel, Lörracherstrasse 50, 4125 Riehen, Switzerland.
Breast Cancer Res. 2007;9(3):R33. doi: 10.1186/bcr1681.
We investigated whether mRNA levels of E2F1, a key transcription factor involved in proliferation, differentiation and apoptosis, could be used as a surrogate marker for the determination of breast cancer outcome.
E2F1 and other proliferation markers were measured by quantitative RT-PCR in 317 primary breast cancer patients from the Stiftung Tumorbank Basel. Correlations to one another as well as to the estrogen receptor and ERBB2 status and clinical outcome were investigated. Results were validated and further compared with expression-based prognostic profiles using The Netherlands Cancer Institute microarray data set reported by Fan and colleagues.
E2F1 mRNA expression levels correlated strongly with the expression of other proliferation markers, and low values were mainly found in estrogen receptor-positive and ERBB2-negative phenotypes. Patients with low E2F1-expressing tumors were associated with favorable outcome (hazard ratio = 4.3 (95% confidence interval = 1.8-9.9), P = 0.001). These results were consistent in univariate and multivariate Cox analyses, and were successfully validated in The Netherlands Cancer Institute data set. Furthermore, E2F1 expression levels correlated well with the 70-gene signature displaying the ability of selecting a common subset of patients at good prognosis. Breast cancer patients' outcome was comparably predictable by E2F1 levels, by the 70-gene signature, by the intrinsic subtype gene classification, by the wound response signature and by the recurrence score.
Assessment of E2F1 at the mRNA level in primary breast cancer is a strong determinant of breast cancer patient outcome. E2F1 expression identified patients at low risk of metastasis irrespective of the estrogen receptor and ERBB2 status, and demonstrated similar prognostic performance to different gene expression-based predictors.
我们研究了E2F1（一种参与增殖、分化和凋亡的关键转录因子）的mRNA水平是否可作为判定乳腺癌预后的替代标志物。
采用定量逆转录聚合酶链反应（RT-PCR）检测了来自巴塞尔肿瘤库的317例原发性乳腺癌患者的E2F1及其他增殖标志物。研究了它们之间的相互关系以及与雌激素受体、ERBB2状态和临床预后的关系。对结果进行了验证，并使用范及其同事报告的荷兰癌症研究所微阵列数据集，进一步与基于表达的预后特征进行了比较。
E2F1 mRNA表达水平与其他增殖标志物的表达密切相关，低水平主要见于雌激素受体阳性和ERBB2阴性表型。E2F1表达低的肿瘤患者预后良好（风险比=4.3（95%置信区间=1.8-9.9），P=0.001）。这些结果在单变量和多变量Cox分析中一致，并在荷兰癌症研究所数据集中得到成功验证。此外，E2F1表达水平与显示选择预后良好的常见患者亚组能力的70基因特征密切相关。E2F1水平、70基因特征、内在亚型基因分类、伤口反应特征和复发评分对乳腺癌患者预后的预测能力相当。
原发性乳腺癌中E2F1 mRNA水平的评估是乳腺癌患者预后的一个重要决定因素。E2F1表达可识别转移风险低的患者，而与雌激素受体和ERBB2状态无关，并显示出与不同基于基因表达的预测指标相似的预后性能。
