A Three-Gene Signature for Outcome in Soft Tissue Sarcoma
A Three-Gene Signature for Outcome in Soft Tissue Sarcoma
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DOI：
10.1158/1078-0432.ccr-08-2534
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发表时间：
2009-08-15
影响因子：
11.5
通讯作者：
Wuerl, Peter
中科院分区：
文献类型：
--
作者：
Hoffman, Andreas-Claudius;Danenberg, Kathleen D.;Wuerl, Peter
目的：寻找标记物或基因集，将进一步将患者分为不同的风险类别，从而允许更个性化的适应多模态治疗方案在软组织肉瘤是必要的。在这项研究中，我们研究了缺氧诱导因子1a（HIF 1a）、肝素结合表皮生长因子样生长因子（HB-EGF）、血管内皮生长因子（VEGF）和其他血管生成相关基因表达的预后价值，以及它们之间的相互关系。福尔马林固定石蜡包埋的组织样本来自45名软组织肉瘤患者（中位年龄57岁，范围16-85岁）。激光捕获显微切割后，直接定量实时逆转录-PCR（TaqMan）分析，一式三份，以确定HIF 1a，HB-EGF，VEGF和其他基因的表达levels.Results：多变量环氧合酶回归分析显示显着的独立协会HB-EGF，HIF 1a，和VEGF-C基因表达的总生存率（P < 0.0001）。这三个基因的综合因素显示，生存期较短的相对风险为5.5，比国际抗癌联盟增加的风险高出两倍多。受试者操作特征曲线分析显示，该因素诊断短（
Purpose: Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1 a (HIF1a), heparin-binding epidermal growth factor-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF), and other angiogenesis-related gene expressions, as well as their interrelationships.Experimental Design: Formalin-fixed paraffin-embedded tissue samples were obtained from 45 patients with soft tissue sarcoma (median age 57 years, range 16-85 years). After laser capture microdissection direct quantitative real-time reverse transcription-PCR (TaqMan) assays were done in triplicates to determine HIF1a, HB-EGF, VEGF, and other gene expression levels.Results: Multivariate cyclooxygenase regression analysis revealed significant independent associations of HB-EGF, HIF1a, and VEGF-C gene expression to the overall survival (P < 0.0001). A combined factor of these three genes showed a relative risk for shorter survival of 5.5, more than twice higher as in an increasing International Union against Cancer Stage. Receiver operating characteristic curve analysis showed a significant sensitivity of 73% and specificity of 82% of this factor for the diagnosis of short (