Filters
Technology
Platform
GSE7895
Homo sapiens
104 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
RNA was obtained from histologically normal bronchial epithelium of never, former, and current smokers undergoing fiberoptic bronchoscopy.
Publication Title
Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We developed a method to convert gene expression signatures across the Illumina and Affymetrix platforms.
Publication Title
Cross-platform prediction of gene expression signatures.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To identify genes expressed during initiation of lung organogenesis, we generated transcriptional profiles of the prospective lung region of the mouse foregut (mid-foregut) microdissected from embryos at three developmental stages between embryonic day 8.5 (E8.5) and E9.5. This period spans from lung specification of foregut cells to the emergence of the primary lung buds. We identified a number of known and novel genes that are temporally regulated as the lung bud forms. Genes that regulate transcription, including DNA binding factors, co-factors, and chromatin remodeling genes, are the main functional groups that change during lung bud formation. Members of key developmental transcription and growth factor families, not previously described to participate in lung organogenesis, are expressed in the mid-foregut during lung bud induction. These studies also show early expression in the mid-foregut of genes that participate in later stages of lung development. This characterization of the mid-foregut transcriptome provides new insights into molecular events leading to lung organogenesis.
Publication Title
Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 75 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A 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
Publication Title
Effects of cigarette smoke on the human airway epithelial cell transcriptome.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: Brainarray Version 11.0.1, HuEx10stv2_Hs_ENTREZG (huex10st), Affymetrix Human Human Exon 1.0 ST Array (huex10st)
Description
Using 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
Publication Title
SIRT1 pathway dysregulation in the smoke-exposed airway epithelium and lung tumor tissue.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Genome-wide studies have identified abundant small, non-coding RNAs including snRNAs, snoRNAs, cryptic unstable transcripts (CUTs), and upstream regulatory RNAs (uRNAs) that are transcribed by RNA polymerase II (pol II) and terminated by a Nrd1-dependent pathway. Here, we show that the prolyl isomerase, Ess1, is required for Nrd1-dependent termination of ncRNAs. Ess1 binds the carboxy terminal domain (CTD) of pol II and is thought to regulate transcription by conformational isomerization of Ser-Pro bonds within the CTD. In ess1 mutants, expression of ~10% of the genome was altered, due primarily to defects in termination of snoRNAs, CUTs, SUTs and uRNAs. Ess1 promoted dephosphorylation of Ser5 (but not Ser2) within the CTD, most likely by the Ssu72 phosphatase, and we provide evidence for a competition between Nrd1 and Pcf11 for CTD-binding that is regulated by Ess1-dependent isomerization. This is the first example of a prolyl isomerase required for interpreting the CTD code.
Publication Title
The Ess1 prolyl isomerase is required for transcription termination of small noncoding RNAs via the Nrd1 pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 192 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
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.
Publication Title
Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 82 Downloadable Samples
IlluminaHiSeq2500
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. Overall design: 82 mRNA-Seq samples from 25 smokers without PMLs, 50 smokers with PMLs, and 7 smokers with metaplasia.
Publication Title
Detecting the Presence and Progression of Premalignant Lung Lesions via Airway Gene Expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 51 Downloadable Samples
- IlluminaHiSeq2500
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. Overall design: 51 mRNA-Seq samples from 23 subjects obtained via bronchscopy (18 subjects with 2 procedures, 5 subjects with 3 procedures).
Publication Title
Detecting the Presence and Progression of Premalignant Lung Lesions via Airway Gene Expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx, Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples