Development of the prediction system for chemosensitivity of Methotrexate, Vinblastine, Doxorubicin, and Cisplatin neoadjuvant chemotherapy in invasive bladder cancer patients

浸润性膀胱癌患者甲氨蝶呤、长春花碱、阿霉素和顺铂新辅助化疗化疗敏感性预测系统的开发

基本信息

批准号：
18591769
负责人：
FUJIOKA Tomoaki
金额：
$ 2.55万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

To predict the efficacy of the M-VAC neoadjuvant chemotherapy for invasive bladder cancers, we previously established the method to calculate the prediction score on the basis of expression profiles of 14 predictive genes. This time, we constructed the prediction system using handy, cheap, real-time PCR method for a clinical application. First, we designed primers and probes that were able to detect 14 genes that strongly related to response of MVAC chemotherapy. Afterwards, expression level of each gene was analyzed by real-time PCR We used CCT6A as internal control. The obtained level of the gene expression was highly correlated with that of microarrays. We did quantitative real-time RT-CR of the 14 predictive genes for 15 learning cases, and calculated the prediction score for each case. When we estimated these scores by the leave-one-out cross validation test, all cases were placed correctly according to their response to M-VAC. We showed further that the responses of test cases were also predicted with accuracy 'lb examine the possibility of adapting our prediction system for clinical use, we attempted to establish a perdiction "card" system using Taqman Low Density Aarray (TLDA; Applied biosystems). We examined the chemosensitivity of 38 cases with the card, and predicted accurately by the sensitivity of 80% or more. We can predict response within one week when we use this card, and technical burden will be reduced. At present, we began a clinical research employing our prediction system with the card. This research is expected to become the precursors of personalized medicine.

为了预测M-VAC新辅助化学疗法对浸润性膀胱癌的功效，我们先前建立了根据14个预测基因的表达谱的计算预测评分的方法。这次，我们使用方便，廉价，实时的PCR方法构建了预测系统，以用于临床应用。首先，我们设计了能够检测到与MVAC化学疗法反应密切相关的14个基因的引物和探针。之后，通过实时PCR分析了每个基因的表达水平，我们将CCT6A用作内部对照。获得的基因表达水平与微阵列高度相关。我们为15个学习案例进行了14个预测基因的定量实时RT-CR，并计算了每种情况的预测评分。当我们通过剩余的交叉验证测试估算这些分数时，所有案例均根据其对M-VAC的响应正确放置。我们进一步表明，还可以预测测试案例的响应，并以准确性的LB检查调整我们的预测系统的临床使用的可能性，我们尝试使用Taqman低密度Aarray（TLDA； Applied Biosystems）来建立一个Perdiction“ Card”系统。我们使用卡片检查了38例38例的化学敏感性，并通过80％或更高的灵敏度准确地预测。我们可以在使用此卡的一周内预测响应，并且技术负担将减轻。目前，我们开始了一项使用该卡的预测系统的临床研究。预计这项研究将成为个性化医学的先驱。