Effect of active smoking on the bronchial epithelium transcriptome
Bibliographic record
Abstract
AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 4994 Background: Tobacco smoke exposure is the major cause of lung cancer. Long term heavy smokers retain an elevated lung cancer risk even years after smoking cessation. Former smokers now account for nearly half of the newly diagnosed lung cancer cases. The mechanism for lung cancer development despite smoking cessation is still poorly understood. In this study, using serial analysis of gene expression (SAGE), we compare the transcriptomes of bronchial cells obtained from current, former and never smokers to identify genes whose expression were reversible and irreversible upon smoking cessation. Objectives: (1) To define the transcriptomes of current, former and never smokers. (2) To identify genes which are dysregulated with active smoking. (3) To identify changes that are irreversible upon smoking cessation. DESIGN, MATERIALS AND METHODS: Twenty-four bronchial epithelial specimens from the peripheral airways obtained during fluorescence bronchoscopy were profiled using SAGE. This sample set was comprised of 8 current smokers, 12 former smokers and 4 never smokers. Transcriptomes for current, former and never smokers were defined using a tag count of ≥2 across all libraries in each set. Genes differentially expressed were identified using the Mann Whitney U test. Select genes were validated in a secondary cohort of 9 current smokers, 7 former smokers and 6 never smokers using quantitative RT-PCR. Results: 3,111,471 SAGE sequence tags representing over 110,000 potentially unique transcripts were generated, representing one of the largest human SAGE studies to date. We identified 1733 genes to be constitutively expressed in current, former and never smoker transcriptomes. Reversible gene expression changes upon smoking cessation were identified, mainly falling into xenobiotic / nucleotide metabolism and muco-ciliary response and clearance. Significantly, altered expression of calcium binding tyrosine-(Y)-phosphorylation regulated (CABYR) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) is reversible upon smoking cessation, neither of which have previously been shown to be expressed in the bronchial epithelium. Conversely, glycogen synthase kinase 3 beta (GSK3B) , mucin 5AC (MUC5AC) demonstrated irreversible expression changes upon smoking cessation. All of these gene expression profiles were validated in a second cohort of samples. Conclusions: Irreversible changes in expression of genes associated with inflammatory pathways and DNA repair may account for substantial DNA damage, and increased susceptibility to lung cancer despite smoking cessation. This work was supported by Genome BC / Genome Canada.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".