权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Construction of gene-expression predictor model for patient outcome with renal cell carcinoma

肾细胞癌患者预后的基因表达预测模型的构建

基本信息

批准号：
18591764
负责人：
YAO Masahiro
金额：
$ 2.49万
依托单位：
Yokohama City 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

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591764/
关键词：
renal cancer clear cell gene expression prognosis diagnosis 転移

项目摘要

Renal cell carcinomas (RCCs) are morphologically and genetically heterogeneous tumors and present diverse clinical courses. We used real-time quantitative PCR to examine the VCAMI and ADFP expression levels of more than 400 clear cell renal carcinomas. We evaluated their significances with respect to patient survival rates using the Cox regression model combined with the split-sample method. We demonstrated that high VCAM1 expression is strongly associated with cancerfine survival for patients with clear cell RCC after curative surgical resection. On the other hand, high ADFPexpression was associated with better cancerspecific survival. Next, We developed a scoring system using levels of gene expression to predict outcome for clear cell RCC patients. We selected differentially expressed genes firom the DNA microarray data of 27clear cell RCCs; 16 were metastasis phenotypes and 11 were not We compared the selected gene set with previously published data and identified 33 overlapping gen … More es closely associated with patient outcome. We selected the 12 top-ranked genes and confirmed the level of expression using quantitative reverse transcriptase PCR Multivariate Cox analysis revealed that three genes-要ascular cell adhesion molecule 1 (VCAM1), endothelin receptor type B (EDNRB), and regulator of G-protein signaling 5 (RGS5)-were the most tightly associated with cancerspecific survival and that higher expression of the three genes correlated with better outcome. A formula for an outcome predictor was generated from integration of the measurements of the expression levels of the three genes. Multivariate Cox models combined with a split-sample cress-validation method in a cohort of 386 clear cell RCC patients demonstrated that the derived score for outcome prediction was an independent predictor in cancerspecific survival tests. The accuracy of the prediction of cancer death after nephrectomy was improved by the inclusion of this score in receiver operating characteristic (ROC) analysis from multivariate logistic regression models, suggesting that a scoring system based on the expression levels of these three genes is useful in the prediction of survival far patients with clear cell RCC. Less

肾细胞癌(RCC)是一种形态和基因上的异质性肿瘤，临床表现多样。我们使用实时荧光定量聚合酶链式反应检测了400多例肾透明细胞癌组织中VCAMI和ADFP的表达水平。我们使用COX回归模型和分裂样本法相结合的方法来评估它们对患者存活率的意义。我们证明VCAM1的高表达与透明细胞肾癌根治性手术切除后肿瘤的良好存活率密切相关。另一方面，ADFP的高表达与更好的癌症特异性生存相关。接下来，我们开发了一个评分系统，使用基因表达水平来预测透明细胞肾癌患者的预后。我们从27例肾透明细胞癌的微阵列数据中筛选出差异表达基因，其中16例为转移表型，11例为非转移表型。将所选基因集与以前发表的数据进行比较，鉴定出33个重叠的基因…更多的ES与患者的预后密切相关。我们选择了排名最靠前的12个基因，并用定量逆转录聚合酶链式反应对其表达水平进行了验证。多变量COX分析显示，要血管细胞黏附分子1(VCAM1)、内皮素B型受体(EDNRB)和G蛋白信号转导调节因子5(RGS5)这三个基因与肿瘤特异性生存关系最为密切，并且这三个基因的高表达与较好的预后相关。结果预测因子的公式是由三个基因表达水平的测量结果整合而成的。在386例透明细胞肾癌患者的队列中，多变量COX模型结合分裂样本CRESS-验证法，结果预测得分在癌症特异性生存试验中是一个独立的预测因子。在多因素Logistic回归模型的受者操作特征(ROC)分析中加入这一评分，提高了预测肾切除后癌症死亡的准确性，表明基于这三个基因表达水平的评分系统在预测远期透明细胞肾癌患者的生存方面是有用的。较少