Validation of Prognostic and Diagnostic molecular tests in Mesothelioma

间皮瘤预后和诊断分子测试的验证

• 批准号: 7081176
• 负责人: RAPHAEL BUENO
• 金额: $ 31.06万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-07 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7081176
• 关键词: biopsy; clinical research; diagnosis; genes; mesothelioma; neoplasm /cancer; prognosis; surgery

DESCRIPTION (provided by applicant): 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 minimally 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 unnecessary and save certain patients from unnecessary 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.

描述（由申请人提供）：恶性胸膜间皮瘤（MPM）是一种高度致命的癌症，目前缺乏有效的治疗方法。即使是这种恶性肿瘤治疗的基本要素，例如方便的诊断和准确的预后，仍然具有挑战性，并且需要积极的手术切除才能明确的分期和预后。我们之前描述了一种新技术，利用基因表达比率将全基因组表达研究转化为临床相关测试，可以准确预测许多临床参数，例如癌症的诊断和预后。具体来说，我们开发了一项测试来区分 MPM 和肺癌，以及另一项测试来预测接受手术的 MPM 患者的结果。这些基于比率的测试需要少量的肿瘤 RNA，以统计显着的方式预测接受 MPM 手术的患者的诊断以及临床结果。我们建议通过识别额外的基因来扩展这些测试的诊断能力，以便在怀疑 MPM 时做出正确的诊断。该方法可以作为基因组的模板。鉴别诊断算法作为病理学的辅助手段。然后，我们将在其他样本上完善和验证这些测试。我们还建议完善和开发该方法，以便能够对微创或使用图像引导细针抽吸获得的标本进行适当的测试。为了将预后和诊断测试带到床边，它们需要与实际的患者管理相关，并进行标准化和验证，最好是在多中心环境中进行验证。我们建议在前瞻性地参加我们机构的临床试验和多中心研究的其他患者中前瞻性地验证细针抽吸和微创活检的预后测试。拟议的工作将利用可以测量整个肿瘤基因组表达（RNA）的新技术来开发可轻松应用于患者的新测试。除了提供新的测试来改变 MPM 患者的管理——最终使诊断手术变得不必要，并使某些患者免于不必要的大手术——这项工作将使我们能够开发一个诊断、预后和治疗指导平台，最终可用于其他癌症和人类疾病，从而实现癌症和其他疾病的个体基因组定向治疗。