Institut Curie, CNRS, Paris, France.
Clin Cancer Res. 2012 Mar 15;18(6):1704-15. doi: 10.1158/1078-0432.CCR-11-1954. Epub 2012 Jan 23.
A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.
Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.
The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.
Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.
先前从一系列 165 例年轻乳腺癌患者中鉴定出了一个预测保乳治疗后局部复发的基因表达特征。我们在另一个平台和独立的系列中评估了这个特征，比较了它与其他已发表的基因集的性能，并研究了更大数据集的基因表达谱。
从最初的 165 例荷兰患者中的 148 例和 195 例法国患者的独立验证系列中获得了基因表达肿瘤谱。使用无监督和有监督分类来研究 343 例乳腺癌的基因表达谱，并确定风险不同的局部复发的亚组。
先前的局部复发特征在不同平台上得到了验证。然而，当应用于法国患者时，该特征并没有重现其报告的性能，并且不能比其他已发表的基因集更好地对患者进行分类。对所有 343 例乳腺癌进行层次聚类并没有显示出任何反映局部复发状态的分组。仅在三阴性肿瘤中，发现与增殖相关的基因在有或无局部复发的患者之间存在差异表达。有监督分类未发现任何可预测局部复发或能够优于基于临床变量的分类的显著基因集。
尽管先前确定的局部复发特征在另一个平台上是稳健的，但我们既不能在独立的数据集上验证它，也不能使用更大的数据集定义一个用于局部复发的强大基因表达分类器。我们得出的结论是，在保乳治疗后有或无局部复发的患者的肿瘤中，基因表达模式没有显著差异。
