Early detection of lung cancer in veterans

退伍军人肺癌的早期发现

• 批准号: 8698379
• 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/8698379
• 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; 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; screening; 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.

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。吸烟是退伍军人中NSCLC的主要原因。同时，吸烟也是慢性阻塞性肺疾病（COPD）的主要原因，COPD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。考虑到晚期NSCLC的预后不良，在重度吸烟者和COPD退伍军人中早期发现NSCLC将降低NSCLC的死亡率。然而，目前的诊断技术要么是侵入性的，要么准确性差。在这里，我们建议开发基于肿瘤的非编码RNA（ncRNA）生物标志物，可以联合收割机与基因组探针用于退伍军人中重度吸烟者和COPD患者的NSCLC早期检测。在此之前，我们改进了痰液诱导方案，建立了富集技术，可以有效地收集深呼吸道上皮细胞用于痰液的分子分析。我们还开发了基于肺癌的基因组探针，与痰液细胞学相比，它可以以更高的灵敏度诊断NSCLC。然而，探针的灵敏度不足以用于临床应用。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是稳定存在于痰液中，并在肺癌的诊断有潜在的用途。此外，我们确定了一组ncRNA的签名，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，并且从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一类生物标志物应该具有以可接受的准确度诊断肺癌的潜力。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NSCLC的早期检测提供一种准确和非侵入性的方法。三个目标是：1，从鉴定的ncRNA特征，优化一组用于早期NSCLC的高度特异性和敏感性的痰生物标志物，2，确定在我们现有的痰标本中使用ncRNA生物标志物与基因组探针用于NSCLC早期检测，3，在独立队列中验证用于NSCLC早期检测的组合策略。完成后，这项工作将为进一步验证生物标志物诊断价值的临床试验奠定坚实的基础。可以在早期阶段识别NSCLC的生物标志物的使用将为恶性肿瘤的有效治疗提供最佳机会，因此将为被诊断患有肺癌的退伍军人提供最好的医疗保健。