Early detection of lung cancer in veterans

退伍军人肺癌的早期发现

• 批准号: 8141598
• 负责人: Feng Jiang
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141598
• 关键词: American Association of Cancer Research; Award; Basic Science; Benign; Biological Assay; Biological Markers; Biometry; Bronchoscopy; Cancer Etiology; Cancer Patient; Cessation of life; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Complex; Data; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Early Diagnosis; Environment; Epithelial Cells; Foundations; Functional RNA; Future; Gene Expression; Genetic screening method; Genomics; Goals; Healthcare; Healthcare Systems; In Situ; Individual; Institutional Review Boards; Interdisciplinary Study; Malignant Neoplasms; Malignant neoplasm of lung; Maryland; MicroRNAs; Microarray Analysis; Mission; Molecular; Molecular Analysis; Molecular Genetics; Mutation; Neoplasms; Non-Small-Cell Lung Carcinoma; Outcome; Pain; Pathology; Patient Care; Patients; Population; Prevention Research; Prevention program; Process; Protocols documentation; Pulmonology; RNA marker; Research; Research Project Grants; Resources; Sampling; Screening procedure; Secure; Sensitivity and Specificity; Small Nucleolar RNA; Smoker; Solid; Specimen; Sputum; Sputum Cytology Screening; Staging; Techniques; Testing; Time; Tobacco smoking; Translating; Translational Research; Universities; Veterans; Woman; Work; Workload; X-Ray Computed Tomography; base; cancer diagnosis; cancer genomics; cancer prevention; clinical application; clinical practice; clinically significant; cohort; cost; disease diagnosis; effective therapy; health administration; improved; innovation; lung cancer screening; medical schools; men; mortality; news; non-smoker; oncology; outcome forecast; prospective; research and development; respiratory; success

DESCRIPTION (provided by applicant): Non-small cell lung cancer (NSCLC) is the number one cancer killer of U.S. Veterans. Tobacco smoking is the major cause of NSCLC among Veterans. Meanwhile, tobacco smoking is also the primary cause of chronic obstructive pulmonary disease (COPD) that is a common benign disease in Veterans. Furthermore, Veterans with COPD are 4-6 times more likely to develop NSCLC than healthy individuals. Given the poor prognosis associated with advanced stage NSCLC, early detection of NSCLC in Veterans who are heavy smokers and have COPD will reduce the mortality from NSCLC. However, the current diagnostic techniques are either invasive or have poor accuracy. Here we propose to develop sputum-based non-coding RNA (ncRNA) biomarkers that can combine with the genomic probes for NSCLC early detection in heavy smokers and COPD patients among Veterans. Previously, we modified sputum induction protocol and established enrichment technique that can efficiently collect deep respiratory epithelial cells for molecular analysis of sputum. We also developed sputum-based genomic probes that can diagnose NSCLC with higher sensitivity compared with sputum cytology. However, the sensitivity of the probes is not high enough for clinical application. NcRNAs, particularly miRNAs, are emerging as potential biomarkers in cancer diagnosis. We recently demonstrated that ncRNAs are stably present in sputum and are potentially useful in diagnosis of lung cancer. Furthermore, we identified a set of ncRNA signatures including 21 miRNAs and five small nucleolar RNAs (snoRNAs) whose altered expressions are associated with early stage NSCLC. Because lung cancer is a heterogeneous disease and develops from a complex and multistep processes, the use of multiple types of biomarkers rather than only one class of biomarkers should have the potential to diagnose lung cancer with acceptable accuracy. Therefore, we hypothesize that analyzing the ncRNAs with the developed genomic probes in sputum will provide an accurate and noninvasive approach for early detection of NSCLC in Veterans. Three Aims are: 1, from the identified ncRNA signatures, optimizing a panel of highly specific and sensitive sputum biomarkers for early stage NSCLC, 2, determining the use of ncRNA biomarkers with genomic probes for NSCLC early detection in our existing sputum specimens, 3, validating the combined strategy for NSCLC early detection in an independent cohort. Upon completion, the work will lay a solid foundation for a clinical trial that will further validate the diagnostic value of the biomarkers. The use of the biomarkers that can identify NSCLC at its early stage will offer the best opportunity for effective treatments of the malignancy, and therefore will provide the best health care for Veterans diagnosed with lung cancer. PUBLIC HEALTH RELEVANCE: Non-small-cell lung cancer (NSCLC) is the number one cancer killer for U.S. Veterans. Veterans who are heavy smokers are up to 75 percent more likely to develop NSCLC than non-smokers. Furthermore, Veterans with chronic obstructive pulmonary disease (COPD) are 4-6 times more likely to develop lung cancer than healthy individuals. Given the poor prognosis associated with advanced stage NSCLC, early detection of the cancer in Veterans who are heavy smokers and have COPD will reduce the mortality from NSCLC. However, the current diagnostic techniques are either invasive or have low accuracy. Here we propose to develop sputum biomarkers that can be used for noninvasively identifying NSCLC earlier from heavy smokers and COPD patients among Veterans. Future application of the biomarkers in clinical settings will provide the best health care for Veterans with lung cancer by dramatically reducing the mortality.

描述（由申请人提供）： 非小细胞肺癌（NSCLC）是美国退伍军人的头号癌症杀手。吸烟是退伍军人患非小细胞肺癌的主要原因。同时，吸烟也是慢性阻塞性肺病（COPD）的主要原因，慢性阻塞性肺病是退伍军人常见的良性疾病。此外，患有 COPD 的退伍军人患 NSCLC 的可能性是健康人的 4-6 倍。鉴于晚期 NSCLC 的预后不良，对重度吸烟者和患有慢性阻塞性肺病 (COPD) 的退伍军人进行早期发现 NSCLC 将降低 NSCLC 的死亡率。然而，当前的诊断技术要么是侵入性的，要么准确性较差。在这里，我们建议开发基于痰的非编码 RNA (ncRNA) 生物标志物，可以与基因组探针结合，用于重度吸烟者和退伍军人中慢性阻塞性肺病患者的 NSCLC 早期检测。此前，我们修改了痰液诱导方案并建立了富集技术，可以有效收集深部呼吸道上皮细胞以进行痰液分子分析。我们还开发了基于痰的基因组探针，与痰细胞学相比，可以以更高的灵敏度诊断 NSCLC。然而，该探针的灵敏度还不够高，无法满足临床应用。 NcRNA，特别是 miRNA，正在成为癌症诊断中的潜在生物标志物。我们最近证明 ncRNA 稳定存在于痰中，并且可能有助于肺癌的诊断。此外，我们还鉴定了一组 ncRNA 特征，包括 21 个 miRNA 和 5 个小核仁 RNA (snoRNA)，其表达改变与早期 NSCLC 相关。由于肺癌是一种异质性疾病，是由复杂的多步骤过程发展而来，因此使用多种类型的生物标志物而不是仅使用一类生物标志物应该有可能以可接受的准确性诊断肺癌。因此，我们假设用开发的基因组探针分析痰液中的 ncRNA 将为退伍军人的 NSCLC 早期检测提供准确且无创的方法。三个目标是：1、根据已识别的 ncRNA 特征，优化一组针对早期 NSCLC 的高度特异性和敏感的痰生物标志物，2、确定使用 ncRNA 生物标志物和基因组探针在我们现有的痰标本中进行 NSCLC 早期检测，3、在独立队列中验证非小细胞肺癌早期检测的联合策略。完成后，这项工作将为临床试验奠定坚实的基础，进一步验证生物标志物的诊断价值。使用能够在早期阶段识别非小细胞肺癌的生物标志物将为有效治疗恶性肿瘤提供最佳机会，因此将为诊断患有肺癌的退伍军人提供最佳的医疗保健。 公共卫生相关性： 非小细胞肺癌（NSCLC）是美国退伍军人的头号癌症杀手。重度吸烟的退伍军人患 NSCLC 的可能性比不吸烟的人高出 75%。此外，患有慢性阻塞性肺病 (COPD) 的退伍军人患肺癌的可能性是健康人的 4-6 倍。鉴于晚期非小细胞肺癌的预后不良，对重度吸烟者和患有慢性阻塞性肺病的退伍军人进行早期发现癌症将降低非小细胞肺癌的死亡率。然而，当前的诊断技术要么是侵入性的，要么准确性较低。在这里，我们建议开发痰生物标志物，可用于早期无创地识别重度吸烟者和退伍军人中慢性阻塞性肺病患者的非小细胞肺癌。生物标记物在临床环境中的未来应用将为患有肺癌的退伍军人提供最佳的医疗保健，显着降低死亡率。