Mining expressed sequence tags identifies cancer markers of clinical interest.

Mining expressed sequence tags identifies cancer markers of clinical interest.
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DOI:
10.1186/1471-2105-7-481
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发表时间:
2006-11-01
期刊:
影响因子:
3
通讯作者:
Skrabanek L
Skrabanek L
中科院分区:
生物学4区
文献类型:
--
作者:
Campagne F;Skrabanek L

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基因表达数据是有关癌症中基因转录失调的丰富信息来源。在癌症中表现出差异调节的基因是癌症生物标志物的一个亚型。我们提出了一种挖掘表达序列标签以发现癌症生物标志物的方法。错误发现率分析表明,当应用于人类和小鼠全基因组筛选时,该方法产生的错误发现率低于 22%。通过这种方法,我们确定了癌症中差异表达最一致的 200 个基因(称为 HM200),并继续表征这些基因。当用于各种癌症分类任务的预测时(在 24 个独立的癌症微阵列数据集中,总共 59 个分类),我们表明 HM200 和较短的基因列表 HM100 是非常有竞争力的癌症生物标志物集。事实上,与 13 个已发布的癌症标记基因列表相比,HM200 在 79% 的考虑分类中实现了最佳或第二好的分类性能。这些结果表明存在至少一种通用癌症标记物集,其预测价值跨越多种肿瘤类型和分类类型。我们与其他标记基因列表的比较表明,HM200 标记物大多是新型癌症标记物。我们还将之前发布的 Pomeroy-400 列表确定为另一个通用癌症标记物集。引人注目的是,Pomeroy-400 有 27 个与 HM200 相同的基因。我们的数据表明,一组核心基因对多种肿瘤类型中涉及肿瘤发生的途径的失调有反应,并且这些基因可以在临床应用中作为转录癌症标记物。最后,我们的研究提出了在微阵列研究中选择和评估癌症生物标志物的新策略。
Gene expression data are a rich source of information about the transcriptional dis-regulation of genes in cancer. Genes that display differential regulation in cancer are a subtype of cancer biomarkers. We present an approach to mine expressed sequence tags to discover cancer biomarkers. A false discovery rate analysis suggests that the approach generates less than 22% false discoveries when applied to combined human and mouse whole genome screens. With this approach, we identify the 200 genes most consistently differentially expressed in cancer (called HM200) and proceed to characterize these genes. When used for prediction in a variety of cancer classification tasks (in 24 independent cancer microarray datasets, 59 classifications total), we show that HM200 and the shorter gene list HM100 are very competitive cancer biomarker sets. Indeed, when compared to 13 published cancer marker gene lists, HM200 achieves the best or second best classification performance in 79% of the classifications considered. These results indicate the existence of at least one general cancer marker set whose predictive value spans several tumor types and classification types. Our comparison with other marker gene lists shows that HM200 markers are mostly novel cancer markers. We also identify the previously published Pomeroy-400 list as another general cancer marker set. Strikingly, Pomeroy-400 has 27 genes in common with HM200. Our data suggest that a core set of genes are responsive to the deregulation of pathways involved in tumorigenesis in a variety of tumor types and that these genes could serve as transcriptional cancer markers in applications of clinical interest. Finally, our study suggests new strategies to select and evaluate cancer biomarkers in microarray studies.
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