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: 7776923
• 负责人: RAPHAEL BUENO
• 金额: $ 30.16万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7776923
• 关键词: Algorithms; Base Ratios; Biopsy; Biopsy Specimen; Clinical; Clinical Trials; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Disease; Elements; Enrollment; Excision; Fine needle aspiration biopsy; Gene Expression; General Anesthesia; Genes; Genetic Transcription; Genome; Genomics; Image; Individual; Institution; Lung Adenocarcinoma; Malignant Neoplasms; Malignant Pleural Mesothelioma; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measures; Mesothelioma; Methodology; Methods; Molecular Diagnostic Testing; Needles; Operative Surgical Procedures; Outcome; Pathologist; Pathology; Patients; Pattern; Pleura; Pleural; Pneumonectomy; RNA; Radiation therapy; Research Personnel; Retrieval; Sampling; Specimen; Staging; Stratification; Techniques; Testing; Time; Tissues; Training; Translating; Treatment Protocols; Validation; Work; cancer therapy; chemotherapy; clinically relevant; cohort; effective therapy; human disease; improved; malignant breast neoplasm; medulloblastoma; miniaturize; minimally invasive; new technology; novel; outcome forecast; prognostic; programs; prospective; tumor

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.

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。 即使是治疗这种恶性肿瘤的基本要素，例如便捷的诊断和准确的治疗， 预后仍然具有挑战性，需要积极的手术切除才能明确分期和 预后。我们之前描述了一种利用基因表达比率来翻译整个基因的新技术 将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，我们开发了一个测试来区分 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诊断以及 接受 MPM 手术的患者的临床结果。 我们建议通过鉴定额外的基因来扩展这些测试的诊断能力 每当怀疑 MPM 时，即可做出正确诊断。该方法可以作为基因组学的模板。 鉴别诊断算法作为病理学的辅助手段。然后我们将完善并验证这些测试 额外的标本。我们还建议完善和开发该方法，以便获得样本 微创或使用图像引导细针抽吸时可以进行适当的测试。 为了将预后和诊断测试带到床边，它们需要与实际患者相关 管理、标准化和验证，最好是在多中心环境中。我们建议 前瞻性验证细针抽吸和微创活检的预后测试 其他患者前瞻性地参加了我们机构的临床试验和多中心研究。 拟议的工作将利用可以测量整个基因表达（RNA）的新技术 肿瘤基因组开发可以轻松应用于患者的新测试。除了提供新的测试 这将改变 MPM 患者的治疗——最终使诊断不需要手术，并且 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种诊断方法， 最终可用于其他癌症和人类的预后和治疗指导平台 疾病，允许个体基因组定向治疗癌症和其他疾病。