Validation of Prognostic and Diagnostic molecular tests in Mesothelioma

恶性胸膜间皮瘤(MPM)是一种高度致命性的癌症，目前缺乏有效的治疗方法。 即使是诊断及时、准确等基本要素也是治疗该病的关键 预后仍然具有挑战性，需要积极的手术切除才能确定分期和 预后。我们之前已经描述了一种新技术，使用基因表达比率来翻译整个 基因组表达研究可以准确预测许多临床参数的临床相关测试 例如癌症的诊断和预后。具体地说，我们开发了一个测试来区分MPM 和肺癌，以及另一项预测接受手术的MPM患者结果的测试。这些基于比率的 检测需要少量的肿瘤RNA，以统计意义上的方式预测诊断以及 接受MPM手术的患者的临床结果。 我们建议通过识别更多的基因来扩大这些测试的诊断能力 只要怀疑MPM，就能正确诊断。这种方法可以作为基因组分析的模板。 鉴别诊断算法作为病理学的辅助手段。然后，我们将改进和验证这些测试 其他标本。我们还建议改进和发展这一方法，以便获得 微创或同时使用图像引导的细针抽吸可进行适当的测试。 为了将预测和诊断测试带到床边，需要使它们与实际患者相关 管理，标准化和验证，最好是在多中心的环境中。我们建议 前瞻性验证细针抽吸和微创活检对预后的影响 在我们机构和一项多中心研究中，有更多的患者预期参加临床试验。 这项拟议中的工作将利用新技术来测量整个基因的表达(RNA) 肿瘤基因组开发新的测试，可以很容易地应用于患者。除了提供新的测试之外 这将改变MPM患者的管理--最终使诊断手术变得不必要和 将某些患者从不必要的大手术中拯救出来--这项工作将使我们能够开发出一种诊断、 最终可用于其他癌症和人类的预后和治疗指导平台 疾病允许个人基因组定向治疗癌症和其他疾病。

Malignant pleural mesothelioma (MPM) is a highly lethal cancer for which effective therapy is lacking. Even the basic elements to treatment for this malignancy such as expedient diagnosis and accurate prognosis remain challenging and aggressive surgical extirpation is required for definitive staging and prognosis. We have previously described a novel technique using gene expression ratios to translate whole genome expression studies into clinically relevant tests that can accurately predict many clinical parameters such as diagnosis and prognosis in cancers. Specifically, we developed a test to distinguish between MPM and lung cancer and another test to,predict outcome in MPM patients undergoing surgery. These ratio-based tests require small amounts of tumor RNA, to predict in a statistically significant manner diagnosis as well as clinical outcome for patients undergoing surgery for MPM. We propose to expand the diagnostic capability of these tests by identifying additional genes to make the correct diagnosis whenever MPM is suspected. This methodology can serve as a template for a genomic . differential diagnosis algorithm to be an adjunct for pathology. We will then refine and validate these tests on additional specimens. We also propose to refine and develop the methodology so that specimens obtained minimally invasively or while using image-guided fine needle aspiration can be appropriately tested. To bring the prognostic and diagnostic tests to bedside they need to be made relevant to actual patient management, be standardized and be validated, preferably in a multi-center setting. We propose to prospectively validate the prognostic tests both with fine needle aspiration and minmally invasive biopsies in additional patients enrolled prospectively in clinical trials at our institution and in a multi center study. The proposed work will capitalize on new technology that can measure the expression (RNA) of the entire tumor genome to develop new tests that can be easily applied to patients. In addition to providing new tests that will alter the management of MPM patients--by eventually making surgery for diagnosis unecessary and save certain patientsfrom unecessary major surgery- this work will allow us to develop a diagnostic, prognostic and treatment directing platform that can be ultimately used for other cancers and human diseases to allow individual genome directed therapy for cancer and other diseases.