Generation of a Concise Gene Panel for Outcome Prediction in Urinary Bladder Cancer
Generation of a Concise Gene Panel for Outcome Prediction in Urinary Bladder Cancer
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DOI：
10.1200/jco.2008.18.5744
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发表时间：
2009-08-20
影响因子：
45.3
通讯作者：
Cote, Richard J.
中科院分区：
文献类型：
--
作者：
Mitra, Anirban P.;Pagliarulo, Vincenzo;Cote, Richard J.
本研究旨在确定分子通路的改变是否可以补充TNM分期以更准确地预测尿路上皮癌(UC)患者的临床预后。所有肿瘤转录值超过两个标准差的正常平均表达被指定为高表达或低表达。进行了单变量和多变量分析，以获得预测性表达特征。结果在单因素分析中，6个基因与复发时间显著相关，10个基因与总生存率显著相关。递归分割确定了三个基因是复发的重要决定因素，三个基因是总存活率的重要决定因素。在通过单变量或分割分析确定的所有基因中，有四个基因被发现同时显著预测复发和生存(Jun、MAP2K6、STAT3和ICAM1)；过度表达与较差的预后相关。比较>；=四分之三的有利(低或正常)表达与
PurposeThis study sought to determine if alterations in molecular pathways could supplement TNM staging to more accurately predict clinical outcome in patients with urothelial carcinoma (UC).Patients and MethodsExpressions of 69 genes involved in known cancer pathways were quantified on bladder specimens from 58 patients with UC (stages Ta-T4) and five normal urothelium controls. All tumor transcript values beyond two standard deviations from the normal mean expression were designated as over- or underexpressed. Univariate and multivariable analyses were conducted to obtain a predictive expression signature. A published external data set was used to confirm the potential of the prognostic gene panels.ResultsIn univariate analysis, six genes were significantly associated with time to recurrence, and 10 with overall survival. Recursive partitioning identified three genes as significant determinants for recurrence, and three for overall survival. Of all genes identified by either univariate or partitioning analysis, four were found to significantly predict both recurrence and survival (JUN, MAP2K6, STAT3, and ICAM1); overexpression was associated with worse outcome. Comparing the favorable (low or normal) expression of >= three of four versus