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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

基本信息

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
项目类别：
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

项目摘要

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.

吸烟是导致肺癌和慢性阻塞性肺疾病的主要原因。在男性和女性的慢性阻塞性肺病（COPD）中，疾病风险和表型的性别差异独立于暴露水平已被观察到。此外，肺癌发病率、存活率、细胞类型和分子生物学特征也与肺癌的发病率、存活率、细胞类型和分子生物学特征相关。缺陷以性别特异性方式不同。同样，肺功能损害的程度、 COPD女性患者支气管肺泡灌洗液中的蛋白质表达不同，对患有这种疾病的人来说。这些观察结果表明，与性别有关的分子过程影响了肺癌和COPD的发展。这份行政补充文件旨在描述性别特异性肺组织和支气管气道上皮中影响肺的基因表达的改变以COPD相关或COPD非依赖的方式致癌。拟议的研究利用作为父母资助NCI 1 R 01 CA 16483 -02的一部分生成的转录组学数据，以及来自相同队列的额外样本，以获得足够的把握度来检测性别特异性导致肺癌发生的基因表达差异。在我们先前工作的基础上证明吸烟相关、肺癌相关和COPD相关基因表达变化在气道上皮“损伤领域”，该建议进一步旨在描述性别特异性对肺的影响，致癌作用延伸到更近端和更容易获得的支气管气道。这些研究将进一步了解性别相关过程对肺癌发展的影响， COPD，并最终允许开发改进的诊断生物标志物，靶向治疗，化学预防策略，可能特别有利于管理这些疾病的妇女。