Expression Signature of E2F1 and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors

Expression Signature of E2F1 and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors
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DOI:
10.1200/jco.2009.25.0977
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发表时间:
2010-06-01
影响因子:
45.3
通讯作者:
Chu, In-Sun
Chu, In-Sun
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Ju-Seog;Leem, Sun-Hee;Chu, In-Sun

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目的大约 20% 的浅表性膀胱肿瘤患者在治疗后进展为浸润性肿瘤。目前前瞻性预测这些肿瘤临床行为的方法是不可靠的。我们的目标是确定一种分子特征,能够可靠地识别患有可能进展为侵袭性肿瘤的高风险浅表肿瘤的患者。患者和方法从 165 名膀胱癌患者的肿瘤标本中收集基因表达数据。应用各种统计方法,包括留一法交叉验证方法,来识别可以预测进展为侵袭性肿瘤的可能性的基因表达特征,并测试独立队列中表达特征的稳健性。基因表达特征的稳健性在独立 (n = 353) 队列中得到验证。结果对基因表达数据的监督分析揭示了与侵袭性膀胱肿瘤密切相关的基因表达特征。基于该基因表达特征的分子分类器正确预测了浅表肿瘤进展为浸润性肿瘤的可能性。结论我们提出了一种分子特征,可以在诊断时预测膀胱癌进展的可能性,并可能改善患者治疗。 J 临床肿瘤杂志 28:2660-2667。 (C) 2010 年美国临床肿瘤学会
PurposeIn approximately 20% of patients with superficial bladder tumors, the tumors progress to invasive tumors after treatment. Current methods of predicting the clinical behavior of these tumors prospectively are unreliable. We aim to identify a molecular signature that can reliably identify patients with high-risk superficial tumors that are likely to progress to invasive tumors.Patients and MethodsGene expression data were collected from tumor specimens from 165 patients with bladder cancer. Various statistical methods, including leave-one-out cross-validation methods, were applied to identify a gene expression signature that could predict the likelihood of progression to invasive tumors and to test the robustness of the expression signature in an independent cohort. The robustness of the gene expression signature was validated in an independent (n = 353) cohort.ResultsSupervised analysis of gene expression data revealed a gene expression signature that is strongly associated with invasive bladder tumors. A molecular classifier based on this gene expression signature correctly predicted the likelihood of progression of superficial tumor to invasive tumor.ConclusionWe present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy. J Clin Oncol 28:2660-2667. (C) 2010 by American Society of Clinical Oncology