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，总的存活率仍然很低。这种癌症每年影响大约3000名美国人，而且其发病率还在上升。MPM的分类和分期很困难，因为有四种不同的分期系统，而正确的组织学亚型往往很难诊断。此外，目前还没有已知的MPM诊断或预后标记物，对这种恶性肿瘤的基因表达了解有限。 在初步实验中，我们使用了基于寡核苷酸的微阵列来评估MPM中的基因表达，并使用实时定量PCR证实了结果。我们已经开发了一个新的基于基因比率的模型，该模型独立于分期、组织学亚型和任何其他已知的临床预测因素，与MPM手术切除后的结果相关。我们已经证明，这种简单的测试可以通过定量实时RT-PCR进行，并根据结果正确地对两组MPM样本进行分类。 这项建议的目标是首先确认和完善我们发现的MPM预后基因比率测试，方法是将其与其他几种此类测试进行比较。然后我们将确定这项测试的重复性、精密度和可变性。我们将论证用微创方法获取这项测试样本的可行性。最后，我们将在一个独立的MPM患者队列中验证改进的基因比预后测试，这些患者的肿瘤和预后数据将被前瞻性地收集。我们将根据存活率和肿瘤进展来确定这项测试在预测预后方面的准确性。

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.