Molecular biomarkers of airway and lung linking COPD and lung cancer

连接慢性阻塞性肺病和肺癌的气道和肺部分子生物标志物

• 批准号: 8604842
• 负责人: Marc Elliott Lenburg
• 金额: $ 10万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604842
• 关键词: Address; Adenocarcinoma; Administrative Supplement; Affect; Biological Markers; Bronchoalveolar Lavage Fluid; Cancer Diagnostics; Cancer Etiology; Carcinogenesis Mechanism; Cessation of life; Chemoprevention; Chronic Obstructive Airway Disease; DNA Methylation; DNA Repair; Data; Defect; Development; Diagnosis; Diagnostic; Disease; Epidemiology; Epithelial; Funding; Gender; Gene Expression; Gene Expression Alteration; Gene Expression Profile; Gene Expression Profiling; Genomics; Impairment; Incidence; Individual; Injury; Knowledge; Lead; Link; Lung; Lung diseases; Malignant neoplasm of lung; Measures; Methylation; Molecular; Morbidity - disease rate; Pathologic; Pathway interactions; Patients; Phenotype; Process; Proteomics; Pulmonary Emphysema; Respiratory System; Respiratory physiology; Respiratory tract structure; Sampling; Site; Smoking; Squamous cell carcinoma; Structure of parenchyma of lung; Tissue Sample; Tissues; Tumor Tissue; United States National Institutes of Health; Woman; Work; airway epithelium; base; cancer cell; cancer chemoprevention; cancer risk; cancer therapy; cell type; cigarette smoking; cigarette smoking; cohort; disease phenotype; disorder risk; improved; insight; lung cancer screening; lung carcinogenesis; men; minimally invasive; mortality; parent grant; protein expression; screening; sex; tool; transcriptomics; tumor

While cigarette smoke exposure is the leading cause of lung cancer and chronic obstructive pulmonary disease (COPD) in both men and women, gender disparities in disease risk and phenotype independent of exposure level have been observed. Moreover, lung cancer incidence, survival, cell-type, and molecular defects differ in a sex-specific manner. Similarly, the degree of lung function impairment, extent of emphysema, and expression of proteins in bronchoalveolar lavage fluid differ in women with COPD compared to men with this disease. These observations suggest that sex-related molecular processes influence the development of lung cancer and COPD. This administrative supplement aims to describe sex-specific alterations of gene expression in lung tissue and the bronchial airway epithelium that influence lung carcinogenesis in a COPD-related or COPD-independent manner. The proposed studies leverage transcriptomic data generated as part of parent grant NCI 1R01CA16483-02, and transcriptomic profiling of additional samples from the same cohorts in order to achieve adequate power to detect sex-specific differences in gene expression that contribute to lung carcinogenesis. Building upon our prior work demonstrating smoking-associated, lung cancer-associated, and COPD-associated gene expression changes in the airway epithelial "field of injury", this proposal further aims to describe sex-specific influences on lung carcinogenesis that extend to the more proximal and easily-obtainable bronchial airway. These studies will further our understanding of the influence of sex-related processes on the development of lung cancer and COPD, and will ultimately allow the development of improved diagnostic biomarkers, targeted therapy, and chemoprevention strategies that may be especially beneficial for managing these diseases in women.

香烟烟雾是肺癌和慢性阻塞性肺的主要原因 男性和女人的疾病（COPD），疾病风险和表型的性别差异与独立于 已经观察到暴露水平。此外，肺癌的发病率，生存率，细胞类型和分子 缺陷在性别特定方式上有所不同。同样，肺功能障碍的程度，程度 COPD女性的支气管肺泡灌洗液中的肺气肿和蛋白质的表达相比 给有这种疾病的男人。这些观察结果表明，与性别相关的分子过程影响 肺癌和COPD的发展。这种行政补充旨在描述特定于性别的 肺组织中基因表达和影响肺的支气管气道上皮的改变 以COPD相关或与COPD无关的方式发生致癌作用。拟议的研究利用 作为父母授予NCI 1R01CA1CA16483-02的转录组数据，以及的转录组分析 来自同一人群的其他样本，以实现足够的能力来检测性别特定的性能 导致肺癌发生的基因表达差异。基于我们先前的工作 证明与吸烟相关，肺癌相关和COPD相关的基因表达变化 在气道上皮“伤害领域”中，该提案进一步旨在描述对肺的特定性影响 致癌作用扩展到更近端且易于吸收的支气管气道。这些研究会 进一步，我们了解与性别相关过程对肺癌发展的影响 COPD，最终将允许改进的诊断生物标志物，有针对性的治疗和 化学预防策略可能特别有益于管理女性中这些疾病。