Cell cycle correlated genes dictate the prognostic power of breast cancer gene lists.
Cell cycle correlated genes dictate the prognostic power of breast cancer gene lists.
复制标题
DOI：
10.1186/1755-8794-1-11
复制
发表时间：
2008-04-25
影响因子：
2.7
通讯作者：
Keri RA
中科院分区：
文献类型：
--
作者：
Mosley JD;Keri RA
许多基因列表或“分类器”已经从全球基因表达数据中获得，这些数据将乳腺癌分为良好和不良预后组。这些分子特征的一个显著特征是它们几乎没有共同的基因，这促使人们猜测它们可能使用不同的基因来测量相同的病理生理过程，例如增殖。然而，这一假设尚未得到严格检验。如果基于基因的分类器通过测量最小数量的细胞过程来起作用，我们假设可以识别这些过程的信息基因，并且可以根据这些基因的预测贡献调整数据集。这样的调整将削弱测量同一过程的任何特征的预测功能。我们直接使用一种新的迭代减法方法来测试这一假设。我们评估了五个基因表达数据集，这些数据集对广泛的乳腺癌亚型进行了采样。在所有数据集中，能够预测转移的主导簇被与细胞周期一致波动的基因大量占据。当检查六个特征良好的分类器时，所有分类器都包含与该聚类相关的基因的比例高于预期。此外，当数据集针对细胞周期簇进行全局调整时，每个分类器都失去了将肿瘤分配到适当的高风险组和低风险组的能力。相比之下，调整其他预测基因簇不会影响它们的表现。这些数据表明，乳腺癌分类器的区分能力取决于与细胞周期进展相关的基因。
Numerous gene lists or "classifiers" have been derived from global gene expression data that assign breast cancers to good and poor prognosis groups. A remarkable feature of these molecular signatures is that they have few genes in common, prompting speculation that they may use distinct genes to measure the same pathophysiological process(es), such as proliferation. However, this supposition has not been rigorously tested. If gene-based classifiers function by measuring a minimal number of cellular processes, we hypothesized that the informative genes for these processes could be identified and the data sets could be adjusted for the predictive contributions of those genes. Such adjustment would then attenuate the predictive function of any signature measuring that same process. We tested this hypothesis directly using a novel iterative-subtractive approach. We evaluated five gene expression data sets that sample a broad range of breast cancer subtypes. In all data sets, the dominant cluster capable of predicting metastasis was heavily populated by genes that fluctuate in concert with the cell cycle. When six well-characterized classifiers were examined, all contained a higher than expected proportion of genes that correlate with this cluster. Furthermore, when the data sets were globally adjusted for the cell cycle cluster, each classifier lost its ability to assign tumors to appropriate high and low risk groups. In contrast, adjusting for other predictive gene clusters did not impact their performance. These data indicate that the discriminative ability of breast cancer classifiers is dependent upon genes that correlate with cell cycle progression.
登录
查看更多内容
影响因子：
4.4
作者：
Sørlie T;Wang Y;Xiao C;Johnsen H;Naume B;Samaha RR;Børresen-Dale AL
通讯作者：
Børresen-Dale AL
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
影响因子：
12.3
作者：
Teschendorff AE;Naderi A;Barbosa-Morais NL;Pinder SE;Ellis IO;Aparicio S;Brenton JD;Caldas C
通讯作者：
Caldas C
影响因子：
11.2
作者：
Dai, HY;van't Veer, L;Friend, S
通讯作者：
Friend, S
影响因子：
158.5
作者：
van de Vijver, MJ;He, YD;Bernards, R
通讯作者：
Bernards, R