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: 7219955
• 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 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7219955
• 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; Invasive; Lung Adenocarcinoma; Malignant Neoplasms; Malignant Pleural Mesothelioma; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measures; Mesothelioma; Methodology; Methods; Molecular Diagnostic Testing; Needles; Numbers; Operative Surgical Procedures; Outcome; Pathologist; Pathology; Patients; Pattern; Pleura; Pleural; Pneumonectomy; RNA; Radiation therapy; Research Personnel; Retrieval; Sampling; Specimen; Staging; Standards of Weights and Measures; Statistically Significant; Stratification; Techniques; Testing; Time; Tissues; Training; Translating; Treatment Protocols; Validation; Work; cancer therapy; chemotherapy; clinically relevant; cohort; human disease; improved; malignant breast neoplasm; medulloblastoma; miniaturize; new technology; novel; outcome forecast; prognostic; programs; prospective; tumor

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，缺乏有效的治疗。即使是治疗这种恶性肿瘤的基本要素，如方便的诊断和准确的预后仍然具有挑战性，并积极的手术切除是必要的明确分期和预后。我们之前已经描述了一种新的技术，使用基因表达比率将全基因组表达研究转化为临床相关的测试，可以准确地预测许多临床参数，如癌症的诊断和预后。具体来说，我们开发了一种区分MPM和肺癌的测试，以及另一种预测接受手术的MPM患者结果的测试。这些基于比率的测试需要少量的肿瘤RNA，以统计学显著的方式预测接受MPM手术的患者的诊断以及临床结果。我们建议扩大这些测试的诊断能力，通过确定额外的基因，以作出正确的诊断时，MPM被怀疑。这种方法可以作为基因组的模板。鉴别诊断算法是病理学的辅助工具。然后，我们将在其他样本上完善和验证这些测试。我们还建议完善和发展的方法，使标本获得微创或同时使用图像引导细针穿刺可以进行适当的测试。为了将预后和诊断测试带到床边，它们需要与实际的患者管理相关，标准化并得到验证，最好是在多中心环境中。我们建议在我们机构的临床试验和多中心研究中前瞻性地招募额外的患者，通过细针穿刺和微创活检来前瞻性地验证预后测试。这项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，开发可以轻松应用于患者的新测试。除了提供将改变MPM患者管理的新测试-通过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种诊断，预后和治疗指导平台，最终可用于其他癌症和人类疾病，以允许癌症和其他疾病的个体基因组定向治疗。