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| Status |
Public on May 25, 2017 |
| Title |
Airway epithelial cells from smokers with and without bronchial premalignant lesions |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
82 mRNA-Seq samples from 25 smokers without PMLs, 50 smokers with PMLs, and 7 smokers with metaplasia.
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| Contributor(s) |
Beane J, Tassinari AM |
| Citation(s) |
28533227 |
| |
| Submission date |
Mar 14, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jennifer Beane |
| E-mail(s) |
jbeane@bu.edu
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| Organization name |
Boston University
|
| Department |
School of Medicine
|
| Lab |
Computational Biomedicine
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| Street address |
72 East Concord Street, E6
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (82)
|
| GSM2088005 |
Subject L12, dysplasia |
| GSM2088006 |
Subject L13, dysplasia |
| GSM2088007 |
Subject L14, dysplasia |
| GSM2088008 |
Subject L15, dysplasia |
| GSM2088009 |
Subject L16, dysplasia |
| GSM2088010 |
Subject L17, dysplasia |
| GSM2088011 |
Subject L18, dysplasia |
| GSM2088012 |
Subject L19, dysplasia |
| GSM2088013 |
Subject L2, no dysplasia |
| GSM2088014 |
Subject L20, no dysplasia |
| GSM2088015 |
Subject L21, dysplasia |
| GSM2088016 |
Subject L22, dysplasia |
| GSM2088017 |
Subject L23, no dysplasia |
| GSM2088018 |
Subject L24, dysplasia |
| GSM2088019 |
Subject L25, no dysplasia |
| GSM2088020 |
Subject L26, no dysplasia |
| GSM2088021 |
Subject L27, no dysplasia |
| GSM2088022 |
Subject L28, no dysplasia |
| GSM2088023 |
Subject L29, dysplasia |
| GSM2088024 |
Subject L3, dysplasia |
| GSM2088025 |
Subject L30, no dysplasia |
| GSM2088026 |
Subject L31, no dysplasia |
| GSM2088027 |
Subject L32, no dysplasia |
| GSM2088028 |
Subject L33, no dysplasia |
| GSM2088029 |
Subject L34, dysplasia |
| GSM2088030 |
Subject L35, dysplasia |
| GSM2088031 |
Subject L36, dysplasia |
| GSM2088032 |
Subject L37, dysplasia |
| GSM2088033 |
Subject L38, no dysplasia |
| GSM2088034 |
Subject L39, dysplasia |
| GSM2088035 |
Subject L4, dysplasia |
| GSM2088036 |
Subject L40, no dysplasia |
| GSM2088037 |
Subject L41, no dysplasia |
| GSM2088038 |
Subject L42, no dysplasia |
| GSM2088039 |
Subject L43, dysplasia |
| GSM2088040 |
Subject L44, dysplasia |
| GSM2088041 |
Subject L45, dysplasia |
| GSM2088042 |
Subject L46, dysplasia |
| GSM2088043 |
Subject L47, dysplasia |
| GSM2088044 |
Subject L48, no dysplasia |
| GSM2088045 |
Subject L49, no dysplasia |
| GSM2088046 |
Subject L5, dysplasia |
| GSM2088047 |
Subject L50, dysplasia |
| GSM2088048 |
Subject L51, no dysplasia |
| GSM2088049 |
Subject L52, no dysplasia |
| GSM2088050 |
Subject L53, dysplasia |
| GSM2088051 |
Subject L54, no dysplasia |
| GSM2088052 |
Subject L55, dysplasia |
| GSM2088053 |
Subject L56, dysplasia |
| GSM2088054 |
Subject L57, dysplasia |
| GSM2088055 |
Subject L58, no dysplasia |
| GSM2088056 |
Subject L59, no dysplasia |
| GSM2088057 |
Subject L6, dysplasia |
| GSM2088058 |
Subject L60, dysplasia |
| GSM2088059 |
Subject L61, dysplasia |
| GSM2088060 |
Subject L62, dysplasia |
| GSM2088061 |
Subject L63, no dysplasia |
| GSM2088062 |
Subject L64, dysplasia |
| GSM2088063 |
Subject L65, dysplasia |
| GSM2088064 |
Subject L66, no dysplasia |
| GSM2088065 |
Subject L67, dysplasia |
| GSM2088066 |
Subject L68, dysplasia |
| GSM2088067 |
Subject L69, no dysplasia |
| GSM2088068 |
Subject L7, dysplasia |
| GSM2088069 |
Subject L70, dysplasia |
| GSM2088070 |
Subject L71, dysplasia |
| GSM2088071 |
Subject L72, dysplasia |
| GSM2088072 |
Subject L73, dysplasia |
| GSM2088073 |
Subject L74, dysplasia |
| GSM2088074 |
Subject L75, dysplasia |
| GSM2088075 |
Subject L76, metaplasia |
| GSM2088076 |
Subject L77, metaplasia |
| GSM2088077 |
Subject L78, metaplasia |
| GSM2088078 |
Subject L79, metaplasia |
| GSM2088079 |
Subject L8, dysplasia |
| GSM2088080 |
Subject L80, metaplasia |
| GSM2088081 |
Subject L81, metaplasia |
| GSM2088082 |
Subject L82, metaplasia |
| GSM2088083 |
Subject L9, dysplasia |
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| This SubSeries is part of SuperSeries: |
| GSE79315 |
Airway epithelial cells obtained via bronchoscopy from high risk subjects with and without bronchial premalignant lesions |
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| Relations |
| BioProject |
PRJNA315161 |
| SRA |
SRP071758 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE79209_L_counts.tsv.gz |
3.2 Mb |
(ftp)(http) |
TSV |
| GSE79209_L_cpm.tsv.gz |
9.4 Mb |
(ftp)(http) |
TSV |
| GSE79209_L_rpkm.tsv.gz |
14.7 Mb |
(ftp)(http) |
TSV |
| GSE79209_L_signal_counts.tsv.gz |
752.2 Kb |
(ftp)(http) |
TSV |
| GSE79209_L_signal_rpkm.tsv.gz |
766.3 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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