RNA was obtained from histologically normal bronchial epithelium of smokers during time of clinical bronchoscopy from relatively accessible airway tissue. Gene expression data from smokers with lung cancer was compared with samples from smokers without lung cancer. This allowed us to generate a diagnostic gene expression profile that could distinguish the two classes. This profile could provide additional clinical benefit in diagnosing cancer amongst smokers with suspect lung cancer.
Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
Sex, Age, Race
View SamplesRNA was obtained from histologically normal bronchial epithelium of never, former, and current smokers undergoing fiberoptic bronchoscopy.
Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression.
Age
View SamplesA number of studies have shown that cigarette smoking produces a field defect, such that genetic mutations induced by smoking occur throughout the lung and its intra and extra-pulmonary airways. Based on this concept, we have begun this study, which has as its goal the definition of the normal airway transcriptome, an analysis of how that transcriptome is affected by cigarette smoke, and to explore the reversibility of altered gene expression when smoking has been discontinued. We have obtained brushings from intra-pulmonary airways (the right upper lobe carina) and scrapings from the buccal mucosa, from normal smoking and non-smoking volunteers (including 34 Current Smokers, 23 Never Smokers and 18 Former Smokers). RNA was isolated from these samples and gene expression profiles from intra-pulmonary airway epithelial cells were analyzed using Affymetrix U133A human gene expression arrays. All microarray data from the experiments described above have been stored, preprocessed and analyzed in a relational MySQL database that is accessible through our website at http://pulm.bumc.bu.edu/aged
Effects of cigarette smoke on the human airway epithelial cell transcriptome.
Sex, Age, Specimen part, Race, Subject
View SamplesPrior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. This study examines the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment showed that the NRF2-mediated antioxidant response pathway differed significantly among these groups.
Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer.
Sex, Age, Specimen part, Race, Subject
View SamplesUsing primary human bronchial epithelial cells collected at bronchoscopy, we have perturbed signaling pathways important in regulation of response to tobacco smoke exposure and cancer development: ATM, BCL2, GPX1, NOS2, IKBKB, and SIRT1
SIRT1 pathway dysregulation in the smoke-exposed airway epithelium and lung tumor tissue.
Specimen part
View SamplesProliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand their relationship to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with ER+ sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by qRT-PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix (ECM) interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and ECM pathways, are dysregulated prior to invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches.
No associated publication
Specimen part, Disease, Disease stage
View SamplesComparison of severely emphysematous tissue removed at lung volume reduction surgery to that of normal or mildly emphysematous lung tissue resected from smokers with nodules suspicious for lung cancer.
No associated publication
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesmRNA expression was assayed from bronchial epithelial cell samples from smokers with and without lung cancer. A subset of the samples (2 of the lung cancer samples and 3 of the no cancer samples) were pooled and underwent whole transcriptome sequencing. The goals were to compare whole transcriptome sequencing gene expression levels to gene expression levels derived from these samples run on the Affymetrix HGU133A 2.0 platform.
Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesComparison of gene and protein expression in the large airway epithelium of never and current smokers.
Comparison of proteomic and transcriptomic profiles in the bronchial airway epithelium of current and never smokers.
Sex, Age, Specimen part, Race, Subject
View Samples