Laas Enora, Mallon Peter, Duhoux Francois P, Hamidouche Amina, Rouzier Roman, Reyal Fabien
Institut Curie, Department of Surgery, Paris, France.
Hopital Tenon, Department of Gynaecologic Surgery, Paris, France.
PLoS One. 2016 Feb 19;11(2):e0148957. doi: 10.1371/journal.pone.0148957. eCollection 2016.
BACKGROUND: Numerous prognostic gene expression signatures have been recently described. Among the signatures there is variation in the constituent genes that are utilized. We aim to evaluate prognostic concordance among eight gene expression signatures, on a large dataset of ER positive HER2 negative breast cancers. METHODS: We analysed the performance of eight gene expression signatures on six different datasets of ER+ HER2- breast cancers. Survival analyses were performed using the Kaplan-Meier estimate of survival function. We assessed discrimination and concordance between the 8 signatures on survival and recurrence rates The Nottingham Prognostic Index (NPI) was used to to stratify the risk of recurrence/death. RESULTS: The discrimination ability of the whole signatures, showed fair discrimination performances, with AUC ranging from 0.64 (95%CI 0.55-0.73 for the 76-genes signatures, to 0.72 (95%CI 0.64-0.8) for the Molecular Prognosis Index T17. Low concordance was found in predicting events in the intermediate and high-risk group, as defined by the NPI. Low risk group was the only subgroup with a good signatures concordance. CONCLUSION: Genomic signatures may be a good option to predict prognosis as most of them perform well at the population level. They exhibit, however, a high degree of discordance in the intermediate and high-risk groups. The major benefit that we could expect from gene expression signatures is the standardization of proliferation assessment.
背景:最近已经描述了许多预后基因表达特征。在这些特征中,所使用的组成基因存在差异。我们旨在评估八个基因表达特征在雌激素受体(ER)阳性、人表皮生长因子受体2(HER2)阴性乳腺癌大型数据集上的预后一致性。 方法:我们分析了八个基因表达特征在ER + HER2 - 乳腺癌六个不同数据集上的表现。使用Kaplan - Meier生存函数估计进行生存分析。我们评估了这8个特征在生存率和复发率方面的区分度和一致性。使用诺丁汉预后指数(NPI)对复发/死亡风险进行分层。 结果:整个特征的区分能力显示出中等的区分性能,曲线下面积(AUC)范围从76基因特征的0.64(95%置信区间0.55 - 0.73)到分子预后指数T17的0.72(95%置信区间0.64 - 0.8)。在由NPI定义的中高风险组中预测事件时发现一致性较低。低风险组是唯一具有良好特征一致性的亚组。 结论:基因组特征可能是预测预后的一个好选择,因为它们中的大多数在总体水平上表现良好。然而,它们在中高风险组中表现出高度的不一致性。我们可以从基因表达特征中期待的主要益处是增殖评估的标准化。
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