A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer.
A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer.
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DOI：
10.1186/bcr2192
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Wessels LF
中科院分区：
文献类型：
--
作者：
Reyal F;van Vliet MH;Armstrong NJ;Horlings HM;de Visser KE;Kok M;Teschendorff AE;Mook S;van 't Veer L;Caldas C;Salmon RJ;van de Vijver MJ;Wessels LF
一些基因表达特征已被提出并证明可预测乳腺癌的预后。在本文中，我们将讨论以下问题：这些签名的执行是否相似？这些签名是否有（共同的）分子过程？能否基于这些已确定的分子过程构建更好的预后预测因子？我们在7个不同的乳腺癌数据集上对9个基因表达特征的表现进行了全面分析。为了更好地表征与这些特征相关的功能过程，我们通过包括与原始特征中至少一个基因显著相关的所有探针来扩大每个特征。使用4个本体数据库评估功能基团的富集程度。九种基因表达特征的分类性能在将样本分配到差结果组或好结果组方面非常相似。然而，在样本水平上分类的一致性很低，只有50%的乳腺癌样本被所有分类器归为同一结果组。预测准确性随着给定样本的不良结果分配的数量而降低。只有良好结果分配的患者组获得了最好的分类表现。扩增特征的富集分析显示11个功能模块具有预后能力。rna剪接和免疫模块的结合导致分类器在独立验证集上具有高预后性能。研究表明，九个特征表现相似，但在预后组分配中表现出很大程度的不一致。功能分析表明，增殖是一个共同的细胞过程，但其他功能类别也丰富，并显示独立的预后能力。我们提供了新的证据，证明免疫和rna剪接过程对乳腺癌的预后有潜在的影响。
Several gene expression signatures have been proposed and demonstrated to be predictive of outcome in breast cancer. In the present article we address the following issues: Do these signatures perform similarly? Are there (common) molecular processes reported by these signatures? Can better prognostic predictors be constructed based on these identified molecular processes? We performed a comprehensive analysis of the performance of nine gene expression signatures on seven different breast cancer datasets. To better characterize the functional processes associated with these signatures, we enlarged each signature by including all probes with a significant correlation to at least one of the genes in the original signature. The enrichment of functional groups was assessed using four ontology databases. The classification performance of the nine gene expression signatures is very similar in terms of assigning a sample to either a poor outcome group or a good outcome group. Nevertheless the concordance in classification at the sample level is low, with only 50% of the breast cancer samples classified in the same outcome group by all classifiers. The predictive accuracy decreases with the number of poor outcome assignments given to a sample. The best classification performance was obtained for the group of patients with only good outcome assignments. Enrichment analysis of the enlarged signatures revealed 11 functional modules with prognostic ability. The combination of the RNA-splicing and immune modules resulted in a classifier with high prognostic performance on an independent validation set. The study revealed that the nine signatures perform similarly but exhibit a large degree of discordance in prognostic group assignment. Functional analyses indicate that proliferation is a common cellular process, but that other functional categories are also enriched and show independent prognostic ability. We provide new evidence of the potentially promising prognostic impact of immunity and RNA-splicing processes in breast cancer.
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DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1073/pnas.0601231103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Ein-Dor, L;Zuk, O;Domany, E
通讯作者：
Domany, E
影响因子：
50.3
作者：
Chin, Koei;DeVries, Sandy;Gray, Joe W.
通讯作者：
Gray, Joe W.
影响因子：
4.4
作者：
Hu, Zhiyuan;Fan, Cheng;Perou, Charles M.
通讯作者：
Perou, Charles M.
影响因子：
8.4
作者：
Dunkler, Daniela;Michiels, Stefan;Schemper, Michael
通讯作者：
Schemper, Michael