EGAS00001002340-sc-2023-03-09T15:04:40Z - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001010122 | EGA |
REPOSITORIES: EGA
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Project description:In this study we aim to characterise the landscape of mutation and clonal selection in normal lung and premalignant lung disease. The study combines targeted sequencing and whole-genome sequencing of microbiopsies of lung and bronchial epithelium. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with premalignant lung disease.
| EGAS00001002340 | EGA
Project description:The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, its precise effects on specific cell types and overall tissue composition are unclear. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses led to the characterization of a set of toxin metabolism genes that localized to smoker ciliated cells, tissue remodeling associated with a loss of club cells and extensive goblet cell hyperplasia, and a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular alterations that may prime the human bronchial epithelium for disease.
2019-09-27 | GSE131391 | GEO
Project description: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. Keywords: Disease state analysis
2006-02-27 | GSE4115 | GEO
Project description:Prior 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. Keywords: Global mRNA expression profiling 21 total arrays (20 unique patients) run on total RNA obtained from Bronchial Epithelium of Smokers with Lung Cancer 30 total arrays (24 unique patients) run on total RNA obtained from Bronchial Epithelium of Smokers without Lung Cancer 9 total arrays (8 unique patients) run on total RNA obtained from Bronchial Epithelium of Never Smokers
2010-09-30 | E-GEOD-19027 | biostudies-arrayexpress
Project description:We have previously shown that gene-expression alterations in cytologically normal appearing bronchial epithelial cells can be used as a biomarker for lung cancer detection in smokers (Whitney et al., BMC Medical Genomics 2015; Silvestri et al., NEJM 2015). In this study, we have established that there are also alterations in bronchial microRNA-expression of smokers with lung cancer. Importantly, the performance of an existing bronchial mRNA-biomarker has been improved by integrating microRNA with mRNA expression.
2018-03-08 | GSE93284 | GEO
Project description:Airway epithelial cells from smokers with and without bronchial premalignant lesions
| PRJNA315161 | ENA
Project description:mRNA expression was profiled from pooled bronchial airway epithelial cell brushings (n=3 patients/pool) obtained during bronchoscopy from healthy never (NS) and current smokers (S) and smokers with (C) and without (NC) lung cancer
2011-06-01 | GSE29006 | GEO
Project description:While lung cancer is the leading cause of cancer death in the US, we have a limited understanding of the earliest molecular events preceding the onset of disease. Prior work has demonstrated that cigarette smoke creates a molecular “field of injury” throughout the airway epithelium and that there are distinct alterations in the airway transcriptome among smokers who have lung cancer. Molecular characterization of this airway “field of injury” in current and former smokers with premalignant lesions (PMLs) could provide novel insights into the earliest molecular events associated with lung carcinogenesis and identify relatively accessible biomarkers to guide lung cancer detection and early intervention. Using mRNA sequencing (mRNA-Seq), we profiled 82 cytologically normal bronchial airway epithelial cells collected during autofluorescence bronchoscopy from high-risk smokers with and without bronchial PMLs, 75 of which were used in downstream analyses. We identified 280 genes differentially expressed in the “field of injury” between subjects with (n=50) and without (n=25) PMLs (FDR<0.002), 81 of which were up-regulated in subjects with PMLs. Oxidative phosphorylation (OXPHOS), the electron transport chain (ETC), and mitochondrial protein transport pathways were strongly enriched among these up-regulated genes (FDR<0.05). We next demonstrated that OXPHOS activation is shared between the “field” and the PMLs with increased oxygen consumption and increased staining for mitochondrial markers in biopsies of PMLs from patients as well as an animal model of lung squamous cell carcinoma (SCC) premalignancy. The 280-gene signature also has a significant concordant relationship to gene expression changes identified in PMLs adjacent to lung SCC tumors, in lung SCC tumors, and in the cytologically normal airway of individuals with lung cancer (FDR<0.05). These findings suggest that these expression changes are reflective of early cancer-associated changes occurring throughout the respiratory tract, and that pathways such as OXPHOS may be targets for chemoprevention. We subsequently developed an airway gene expression biomarker that predicts the presence of PMLs (AUC=0.92, n=17 samples in test set) and show that changes in the biomarker score are associated with progression and regression of PMLs in an independent cohort (AUC=0.75, n=51 samples). The biomarker results indicate that molecular alterations in the field of injury are dynamic with progression or regression of PMLs, suggesting that these changes may be leveraged to stratify high-risk smokers with progressive disease into early intervention trials and monitor disease progression or recurrence.
2017-05-25 | GSE79209 | GEO
Project description:While lung cancer is the leading cause of cancer death in the US, we have a limited understanding of the earliest molecular events preceding the onset of disease. Prior work has demonstrated that cigarette smoke creates a molecular “field of injury” throughout the airway epithelium and that there are distinct alterations in the airway transcriptome among smokers who have lung cancer. Molecular characterization of this airway “field of injury” in current and former smokers with premalignant lesions (PMLs) could provide novel insights into the earliest molecular events associated with lung carcinogenesis and identify relatively accessible biomarkers to guide lung cancer detection and early intervention. Using mRNA sequencing (mRNA-Seq), we profiled cytologically normal bronchial airway epithelial cells collected during autofluorescence bronchoscopy from high-risk smokers (n=75) with and without bronchial PMLs. We identified 280 genes differentially expressed in the “field of injury” between subjects with (n=50) and without (n=25) PMLs (FDR<0.002), 81 of which were up-regulated in subjects with PMLs. Oxidative phosphorylation (OXPHOS), the electron transport chain (ETC), and mitochondrial protein transport pathways were strongly enriched among these up-regulated genes (FDR<0.05). We next demonstrated that OXPHOS activation is shared between the “field” and the PMLs with increased oxygen consumption and increased staining for mitochondrial markers in biopsies of PMLs from patients as well as an animal model of lung squamous cell carcinoma (SCC) premalignancy. The 280-gene signature also has a significant concordant relationship to gene expression changes identified in PMLs adjacent to lung SCC tumors, in lung SCC tumors, and in the cytologically normal airway of individuals with lung cancer (FDR<0.05). These findings suggest that these expression changes are reflective of early cancer-associated changes occurring throughout the respiratory tract, and that pathways such as OXPHOS may be targets for chemoprevention. We subsequently developed an airway gene expression biomarker that predicts the presence of PMLs (AUC=0.92, n=17 samples in test set) and show that changes in the biomarker score are associated with progression and regression of PMLs in an independent cohort (AUC=0.75, n=51 samples). The biomarker results indicate that molecular alterations in the field of injury are dynamic with progression or regression of PMLs, suggesting that these changes may be leveraged to stratify high-risk smokers with progressive disease into early intervention trials and monitor disease progression or recurrence.
2017-05-25 | GSE79210 | GEO
Project description:70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor b, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD. Lung tissue from smokers with no evidence of obstructive lung disease and smokers with COPD was examined for miRNA and mRNA expression followed by validation. We then examined both miRNA and mRNA expression to enrich for relevant biological pathways
2012-06-26 | E-GEOD-38974 | biostudies-arrayexpress