Teschendorff Andrew E, Naderi Ali, Barbosa-Morais Nuno L, Pinder Sarah E, Ellis Ian O, Aparicio Sam, Brenton James D, Caldas Carlos
Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Center, Hills Road, Cambridge CB2 2XZ, UK.
Genome Biol. 2006;7(10):R101. doi: 10.1186/gb-2006-7-10-r101. Epub 2006 Oct 31.
A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer.
Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation.
The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors.
在乳腺癌等异质性疾病中,一种达成共识的预后基因表达分类器仍然难以捉摸。
在此,我们对三个主要的乳腺癌微阵列数据集进行了联合分析,以确定雌激素受体(ER)阳性肿瘤中普遍有效的预后分子分类器。使用最近开发的一种稳健的预后分离测量方法,我们在三个外部独立队列中进一步验证了该预后分类器,在总共877个ER阳性样本中证实了我们分子分类器的有效性。此外,我们发现分子分类器可能并不优于经典预后指标,但它们可用于混合分子病理分类方案以改善预后分离。
这里提出的预后分子分类器是首个在超过877个ER阳性乳腺癌样本以及跨越三个不同微阵列平台上有效的分类器。需要开展更大规模的多机构研究,以充分确定分子分类器与标准预后因素联合使用时所增加的预后价值。