Gene Ratio Based Prognosis in Mesothelioma

描述（由申请人提供） 恶性胸膜间皮瘤（MPM）是一种致命的胸膜恶性肿瘤，目前几乎没有有效的治疗方法，总体生存率仍然很低。这种癌症每年影响大约3，000名美国人，其发病率正在上升。分类和分期是困难的，因为有四个不同的分期系统和正确的组织学亚型的MPM往往很难诊断。此外，没有已知的诊断或预后标记MPM和有限的知识，在这种恶性肿瘤的基因表达。 在初步的实验中，我们已经使用基于谷胱甘肽的微阵列来评估MPM中的基因表达，并使用真实的时间定量PCR证实了结果。我们已经开发了一种新的基于基因比率的模型，该模型与MPM手术切除后的结果相关，独立于分期、组织学亚型和任何其他已知的临床预测因子。我们已经证明，这种简单的测试可以通过定量真实的时间RT-PCR进行，并正确分类的两个队列的MPM标本的基础上的结果。 这个建议的目的是首先确认和完善我们发现的MPM的预后基因比测试，通过比较它与其他几个这样的测试。然后，我们将确定本试验的重现性、精密度和变异性。我们将证明通过微创方法获得用于该测试的样本的可行性。最后，我们将在一个独立的MPM患者队列中验证精确的基因比率预后检验，前瞻性地收集这些患者的肿瘤和预后数据。我们将确定该测试在预测预后（定义为生存期和肿瘤进展）方面的准确性。

DESCRIPTION (provided by applicant) Malignant pleural mesothelioma (MPM) is a lethal malignancy of the pleura for which there is little effective therapy and overall survival remains dismal. This cancer affects approximately 3,000 Americans per year and its incidence is rising. Classification and staging is difficult because there are four different staging systems and the correct histological subtype of MPM is often difficult to diagnose. In addition, there are no known diagnostic or prognostic markers for MPM and limited knowledge of gene expression in this malignancy. In preliminary experiments, we have used oligonucleotide-based microarrays to evaluate gene expression in MPM and confirmed the results using real time quantitative PCR. We have developed a new gene ratio based model that correlates with outcome after surgical resection for MPM independently from stage, histologic subtype and any other known clinical predictor. We have demonstrated that this simple test can be performed by quantitative real time RT-PCR and correctly classified two cohorts of MPM specimens based on outcome. The goal of this proposal is to first confirm and refine the prognostic gene-ratio test that we discovered for MPM by comparing it to several others such tests. We will then determine the reproducibility, precision and variability of this test. We will demonstrate the feasibility of obtaining the samples for this test with minimally invasive methods. Finally we will validate the refined gene ratio prognostic test in an independent cohort of MPM patients from whom tumor and outcome data will be collected prospectively. We will determine the accuracy of this test in predicting outcome as defined by survival and tumor progression.