Outcome signature genes in breast cancer: is there a unique set?
Outcome signature genes in breast cancer: is there a unique set?
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DOI：
10.1093/bioinformatics/bth469
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发表时间：
2005-01-15
期刊：
影响因子：
5.8
通讯作者：
Domany, E
中科院分区：
文献类型：
--
作者：
Ein-Dor, L;Kela, I;Domany, E
目的：预测原发性恶性肿瘤组织的转移潜能直接关系到治疗方法的选择。几个微阵列研究产生的基因集，其表达谱成功地预测生存。然而，这些基因组之间的重叠几乎为零。在其他复杂疾病中也观察到这种微小的重叠，可以解释这种差异的变量引起了广泛的兴趣。在这种情况下，一个主要的开放性问题是是否可以只归因于微不足道的原因，如不同的技术，不同的患者和不同类型的analysis.Results：为了回答这个问题，我们集中在一个单一的乳腺癌数据集，并分析了它由一个单一的方法，这是由范特维尔等人使用的一个。我们发现，事实上，所得到的基因集并不是唯一的;它受到用于基因选择的患者子集的强烈影响。同样的分析也可以产生许多同样具有预测性的列表。数据的三个主要特性解释了这种敏感性：（1）许多基因与生存相关;（2）这些相关性之间的差异很小;（3）当对不同的患者子集进行测量时，相关性波动很大。一个可能的生物学解释这些属性进行了讨论。
Motivation: Predicting the metastatic potential of primary malignant tissues has direct bearing on the choice of therapy. Several microarray studies yielded gene sets whose expression profiles successfully predicted survival. Nevertheless, the overlap between these gene sets is almost zero. Such small overlaps were observed also in other complex diseases, and the variables that could account for the differences had evoked a wide interest. One of the main open questions in this context is whether the disparity can be attributed only to trivial reasons such as different technologies, different patients and different types of analyses.Results: To answer this question, we concentrated on a single breast cancer dataset, and analyzed it by a single method, the one which was used by van't Veer et al. to produce a set of outcome-predictive genes. We showed that, in fact, the resulting set of genes is not unique; it is strongly influenced by the subset of patients used for gene selection. Many equally predictive lists could have been produced from the same analysis. Three main properties of the data explain this sensitivity: (1) many genes are correlated with survival; (2) the differences between these correlations are small; (3) the correlations fluctuate strongly when measured over different subsets of patients. A possible biological explanation for these properties is discussed.