Genome-wide screening of transcriptional modulation in non-smoking female lung cancer in Taiwan
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19804 | GEO | 2011/01/30
SECONDARY ACCESSION(S): PRJNA153899
REPOSITORIES: GEO
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Project description:Although smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of cigarette smoking, extremely lower than those in Caucasian females. This report is a comprehensive analysis of the molecular signature of non-smoking female lung cancer in Taiwan. RNA was extracted from paired tumor and normal tissues for gene expression analysis.
2011-01-30 | E-GEOD-19804 | biostudies-arrayexpress
Project description:Genome-Wide Screening of Genomic Alterations and Transcriptional Modulation in Non-Smoking Female Lung Cancer in Taiwan Sixty-one pairs of cancer and normal lung tissue specimens from non-smoking females were collected at National Taiwan University Hospital and Taichung Veterans General Hospital. The selection criteria of clinical specimens depend on pathology report, physical examination and cigarette-smoking history. Surgical lung tissue specimens were immediately snap-frozen in liquid N2 and stored at -80 °C. Surgical specimens would be further processed for RNA and DNA extraction. Only those samples passed quality controls were processed for gene expression profiling analysis and single nucleotide polymorphism (SNP) analysis respectively.
2012-12-31 | E-GEOD-33355 | biostudies-arrayexpress
Project description:Genome-Wide Screening of Genomic Alterations and Transcriptional Modulation in Non-Smoking Female Lung Cancer in Taiwan
2012-12-31 | GSE33355 | GEO
Project description:Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and Benzo(α)pyrene (BaP) are two major carcinogens in cigarette smoke and have not been tested in models that mimic inhaled exposure for prolonged periods of time. We treated ICR mice with intratracheal delivery of NNK and BaP three times a week for 18 months to mimic chronic smoking exposure. Mice developed epithelial dysplasia followed by lung cancers at increased rates relative to controls. Histology revealed myeloid inflammation in murine lung tissues. Exposure of lung epithelial cells to cigarette smoking condensate led to increased production of pro-inflammatory IL-1. Downstream mediator of IL-1β signaling, Interleukin 1 receptor associated kinase–4 (IRAK4), was overexpressed in murine lung tissues exposed to carcinogens in vivo. Two-thirds of human lung cancer samples also exhibited overactivated IRAK4 expression. IRAK4 was found to localize in microtubules in lung cancer cell lines. Using mass spectrometry on isolated microtubules, we observed that IRAK4 inhibition was associated with decreased phosphorylation of tubular motility proteins including MYH9. Inhibition of IRAK4 resulted in decreased invasion in lung cancer cell lines and reduced growth of lung cancer xenografts. These data demonstrate that smoking associated carcinogens cause myeloid inflammation that can be linked to oncogenic transformation via IRAK4 activation.
2024-10-23 | PXD053181 | Pride
Project description:Aging involves multiple biologically complex processes characterized by a decline in cellular homeostasis over time leading to a loss and impairment of physiological integrity and function. Specific cellular hallmarks of aging include abnormal gene expression patterns, shortened telomeres and associated biological dysfunction. Like all organs, the lung demonstrates both physiological and structural changes with age that result in a progressive decrease in lung function in healthy individuals. Cigarette smoking accelerates lung function decline over time, suggesting smoking accelerates aging of the lung. Based on this data, we hypothesized that cigarette smoking accelerates the aging of the small airway epithelium, the cells that take the initial brunt of inhaled toxins from the cigarette smoke and one of the primary sites of pathology associated with cigarette smoking. Using the sensitive molecular parameters of aging-related gene expression and telomere length, the aging process of the small airway epithelium was assessed in age matched healthy nonsmokers and healthy smokers with no physical manifestation of lung disease or abnormalities in lung function. Analysis of a 73 gene aging signature demonstrated that smoking significantly dysregulates 18 aging-related genes in the small airway epithelium. In an independent cohort of male subjects, smoking significantly reduced telomere length in the small airway epithelium of smokers by 14% compared to nonsmokers. These data provide biologic evidence that prior to the clinical manifestation of lung disease; smoking accelerates aging of the small airway epithelium.
2015-08-17 | GSE52237 | GEO
Project description:Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status. Results: We discovered novel and distinct smoking-status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking-dependent manner. Conclusions: We conclude that miRNAs disrupted in a smoking-status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention.
2014-10-30 | GSE62182 | GEO
Project description:Although smoking-induced lung disease tends to be more common in the upper lobe, it is not known if this results from the skewed distribution of inhaled cigarette smoke or increased susceptibility of the upper lobes to these disorders. The distribution of inhaled cigarette smoke within the lung is complex, depending on lung pressure-volume relationships, gravity, individual smoking habits and the properties of the individual components of cigarette smoke. With the knowledge that the small airway epithelium is the earliest site of smoking-induced lung disease, and that the small airway epithelium is acutely sensitive to inhaled cigarette smoke with significant changes in the up- and down-regulation of hundreds of genes, we compared upper vs lower lobe gene expression in the small airway epithelium of the same cigarette smokers to determine if the gene expression patterns were similar or different. Active smokers (n=11) with early evidence of smoking-induced lung disease (normal spirometry but low diffusing capacity) underwent bronchoscopy and brushing of the small airway epithelium to compare upper vs lower lobe genome-wide gene expression assessed by microarray. Interestingly, cluster and principal component analysis demonstrated that, for each individual, the expression of the known small airway epithelium smoking-responsive genes were remarkably similar as upper vs lower lobe pairs, although, as expected, there were differences in the smoking-induced changes in gene expression from individual to individual. Thus, while there may be topographic differences in the distribution of cigarette smoke, sufficient smoke reaches the upper vs lower lobe small airway epithelium so that, within each smoker, the upper vs lower lobe gene expression are similar. These observations support the concept that the topographic differences in the occurrence of the smoking-induced lung diseases are likely secondary to topographic differences in the susceptibility of the upper vs lower lobes to cigarette smoke, not the topographic differences in distribution of inhaled cigarette smoke.
2017-03-08 | GSE26307 | GEO
Project description:Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status. Results: We discovered novel and distinct smoking-status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking-dependent manner. Conclusions: We conclude that miRNAs disrupted in a smoking-status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention. We applied a whole transcriptome sequencing based approach to interrogate miRNA levels in 94 patient-matched lung adenocarcinoma and non-malignant lung parenchymal tissue pairs from current [CS], former [FS] and never smokers [NS].
2014-10-30 | E-GEOD-62182 | biostudies-arrayexpress
Project description:B cells were found to be directly associated with the onset and development of many smoking-induced diseases. However, the in vivo molecular response of B cells underlying the female cigarette smoking remains unknown. Using the genome-wide Affymetrix HG-133A GeneChip® microarray, we compared the gene expression profiles of peripheral circulating B cells between 39 smoking and 40 non-smoking healthy US white females.
2009-12-25 | GSE18723 | GEO
Project description:Genome-wide screening of genomic alterations and transcriptional modulation in non-smoking female lung cancer in Taiwan
| PRJNA148853 | ENA