Detection of Lung Cancer Risks for Serum Metabolomics

血清代谢组学检测肺癌风险

• 批准号: 7787700
• 负责人: Leo L Cheng
• 金额: $ 24.77万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7787700
• 关键词: Adenocarcinoma; Biochemistry; Biological; Blood; Blood Tests; Blood specimen; Cancer Control; Cancer Detection; Cancer Intervention and Surveillance Modeling Network; Cancer Patient; Cancerous; Cardiac Output; Clinic; Clinical; Coupled; Data; Detection; Development; Diagnosis; Disease; Eligibility Determination; Future; General Population; Genomics; Goals; Histopathology; Knowledge; Lesion; Lung; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Metabolic; Methods; Modeling; Monitor; Non-Small-Cell Lung Carcinoma; Pathology; Patients; Positron-Emission Tomography; Reading; Reporting; Research; Resources; Risk; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Specimen; Squamous cell carcinoma; Staging; Structure of parenchyma of lung; Survival Rate; Symptoms; Techniques; Testing; Time; Tissues; base; cancer proteomics; cancer risk; cancer type; clinical application; cost; design; disorder control; economic outcome; health economics; innovation; lung cancer screening; member; metabolomics; mortality; prevent; public health relevance; research study; success; tool

DESCRIPTION (provided by applicant): The alarmingly high lung cancer mortality rate is due mostly to the lack of effective screening protocols for the general public that can detect and diagnose the condition at early and asymptomatic stages. Current radiological examinations, including CT, MRI, and PET, can detect lesions in the lungs; however, their extremely high costs coupled with their unproven efficacies as screening tools have prevented their use in annual screening protocols for the general public. Analyses of blood samples may be a practical and acceptable resource for advancements in lung cancer screening that can advise patients with suspicious readings to seek immediate further radiological tests. In the era of genomics and proteomics, cancer metabolomics collectively evaluate the biological statuses of global metabolite alterations related to malignancy development and progression. Metabolomic profiles measured from cancerous tissues have shown better sensitivity in assessing patient clinical conditions than current histopathology. The aim of the proposed project is to establish lung cancer specific blood serum metabolomic profiles with enough sensitivity and specificity to indicate the necessity for further radiological tests. In this preliminary and exploratory study, we will analyze paired tissue and serum specimens from the same lung cancer patients by using a magnetic resonance spectroscopy method that we developed for intact specimen analyses, search and discover lung cancer tissue metabolomic profiles in connection with tissue pathologies, apply the parameters of these metabolomic profiles obtained from tissue to their corresponding serum spectroscopic data, and test these calculated serum profiles for their ability to identify and group cancer patients. The project is designed to test the hypothesis that serum metabolomic profiles calculated from tissue metabolomic profiles and corrected by quantitative tissue pathologies may have clinical applicability as an early lung cancer screening test for the general public prior to the development of disease symptoms. The specific aims of the project are: 1) To establish serum metabolomic profiles according to tissue metabolomic profiles measured from the same patients for SCC and adenocarcinoma; and 2) to evaluate the sensitivity and specificity of the established serum metabolite profiles for detection and categorization of lung cancers from these patients, and assess and evaluate the clinical utility of the researched lung cancer serum metabolomic marker for screening, using a model from the NCI's Cancer Intervention and Surveillance Modeling Network (CISNET). PUBLIC HEALTH RELEVANCE: This is an exploratory study of paired tissue and serum samples from various lung cancer patients. If successful, annual screening of serum metabolomic profiles established through the initiatives of this project will direct patients with suspicious serum profiles to advanced and expensive radiological tests to detect lung cancers at early and asymptomatic stages, and in turn increase overall patient survival rates and change the paradigm of current oncological clinics.

描述（由申请人提供）：肺癌死亡率高得惊人，主要是由于缺乏针对公众的有效筛查方案，无法在早期和无症状阶段检测和诊断肺癌。目前的放射学检查，包括CT、MRI和PET，可以检测肺部病变；然而，其极高的成本加上其作为筛查工具的功效未经证实，阻碍了其在公众年度筛查方案中的使用。血液样本分析可能是肺癌筛查进步的实用且可接受的资源，可以建议读数可疑的患者立即寻求进一步的放射学检查。在基因组学和蛋白质组学时代，癌症代谢组学共同评估与恶性肿瘤发生和进展相关的整体代谢物改变的生物学状态。与目前的组织病理学相比，从癌组织中测量的代谢组学谱在评估患者临床状况方面表现出更好的敏感性。该项目的目的是建立肺癌特异性血清代谢组学特征，具有足够的敏感性和特异性，以表明进一步放射学测试的必要性。在这项初步和探索性研究中，我们将使用我们为完整样本分析开发的磁共振波谱方法来分析来自同一肺癌患者的配对组织和血清样本，搜索和发现与组织病理学相关的肺癌组织代谢组图谱，将从组织获得的这些代谢组学特征的参数应用于相应的血清光谱数据，并测试这些计算出的血清特征识别和分组癌症患者的能力。该项目旨在检验以下假设：根据组织代谢组图谱计算并通过定量组织病理学校正的血清代谢组学图谱可能具有临床适用性，可作为公众在疾病症状出现之前的早期肺癌筛查测试。该项目的具体目标是： 1) 根据对同一鳞状细胞癌和腺癌患者测量的组织代谢组学概况，建立血清代谢组学概况； 2) 评估已建立的血清代谢物谱对这些患者肺癌检测和分类的敏感性和特异性，并使用 NCI 的模型评估和评估所研究的肺癌血清代谢组标记物用于筛查的临床效用癌症干预和监测建模网络 (CISNET)。 公共卫生相关性：这是一项对来自不同肺癌患者的配对组织和血清样本的探索性研究。如果成功，通过该项目的举措建立的血清代谢组学特征年度筛查将指导血清特征可疑的患者进行先进且昂贵的放射学检测，以在早期和无症状阶段检测肺癌，从而提高患者的总体生存率并改变当前肿瘤临床的范例。