Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers
Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers
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DOI：
10.1158/1535-7163.mct-05-0408
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发表时间：
2006-03-01
影响因子：
5.7
通讯作者：
Nishiyama, M
中科院分区：
文献类型：
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作者：
Komatsu, M;Hiyama, K;Nishiyama, M
我们试图使用一种新的统计分析来识别有效的标记基因，并基于一组铂和紫杉醇的关键药物敏感性基因的表达分析可以使我们预测对组合的治疗反应的假设，开发了一种预测卵巢癌患者对铂/紫杉醇联合化疗的个体反应的系统。从10株人卵巢癌细胞系中筛选出与顺铂（CDDP）和紫杉醇细胞毒性相关的基因。我们首先从22个已知的敏感性决定基因中选择了5个可靠的预测标记，然后通过使用寡核苷酸微阵列表达数据的二维混合正态模型确定了另外8个新基因。使用通过实时逆转录-PCR定量的基因表达数据，我们固定了最佳线性模型，该模型将定量表达数据转换为每种药物的IC50。对筛选出的基因进行多元回归分析，得到三个预测顺铂和紫杉醇体外活性的公式。以同样的方式，使用体外选择的相同基因，我们尝试开发铂/紫杉醇组合的无进展生存期的预测公式。因此，我们使用不同的13个选择的标记基因（5个已知基因和8个新基因）的集合构建了可能的公式：使用另外9个测试样本的效用确认分析似乎表明，单独使用8个新标记基因的集合的公式可以准确地预测无进展生存期（r = 0.683; P = 0.042）。
We attempted to identify potent marker genes using a new statistical analysis and developed a prediction system for individual response to platinum/paclitaxel combination chemotherapy in ovarian cancer patients based on the hypothesis that expression analysis of a set of the key drug sensitivity genes for platinum and paclitaxel could allow us to predict therapeutic response to the combination. From 10 human ovarian cancer cell lines, genes correlative in the expression levels with cytotoxicities of cisplatin (CDDP) and paclitaxel were chosen. We first selected five reliable prediction markers for the two drugs from 22 genes already known as sensitivity determinants and then identified another 8 novel genes through a two-dimensional mixed normal model using oligomicroarray expression data. Using expression data of genes quantified by real-time reverse transcription-PCR, we fixed the best linear model, which converted the quantified expression data into an IC50 of each drug. Multiple regression analysis of the selected genes yielded three prediction formulae for in vitro activity of CDDP and paclitaxel. In the same way, using the same genes selected in vitro, we then attempted to develop prediction formulae for progression-free survival to the platinum/paclitaxel combination. We therefore constructed possible formulae using different sets of 13 selected marker genes (5 known and 8 novel genes): Utility confirmation analyses using another nine test samples seemed to show that the formulae using a set of 8 novel marker genes alone could accurately predict progression-free survival (r = 0.683; P = 0.042).