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GSE20189
Homo sapiens
160 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Affordable early screening in subjects with high risk of lung cancer has great potential to improve survival from this deadly disease. We measured gene expression from lung tissue and peripheral whole blood (PWB) from adenocarcinoma cases and controls to identify dysregulated lung cancer genes that could be tested in blood to improve identification of at-risk patients in the future. Genome-wide mRNA expression analysis was conducted in 153 subjects (73 adenocarcinoma cases, 80 controls) from the Environment And Genetics in Lung cancer Etiology (EAGLE) study using PWB and paired snap-frozen tumor and non-involved lung tissue samples. Analyses were conducted using unpaired t-tests, linear mixed effects and ANOVA models. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the identified biomarkers. We identified 50 dysregulated genes in stage I adenocarcinoma versus control PWB samples (False Discovery Rate 0.1, fold change 1.5 or 0.66). Among them, eight (TGFBR3, RUNX3, TRGC2, TRGV9, TARP, ACP1, VCAN, and TSTA3) differentiated paired tumor versus non-involved lung tissue samples in stage I cases, suggesting a similar pattern of lung cancer-related changes in PWB and lung tissue. These results were confirmed in two independent gene expression analyses in a blood-based case-control study (n=212) and a tumor-non tumor paired tissue study (n=54). The eight genes discriminated patients with lung cancer from healthy controls with high accuracy (AUC=0.81, 95% CI=0.74-0.87). Our finding suggests the use of gene expression from PWB for the identification of early detection markers of lung cancer in the future.
Publication Title
A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 107 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change>1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p=0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers. Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.
Publication Title
Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
FADD-IEC KO and CASP8 IEC-KO mice spontaneously develop chronic colitis charcterized by inflammatory gene expression. We characterized the role of MLKL, RIPK3, ZBP1, in the upregulation of inlflammatory genes in these mice.
Publication Title
FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 45 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
FADD-IEC KO and CASP8 IEC-KO mice spontaneously develop chronic ileitis charcterized by inflammatory gene expression. We characterized the role of MLKL, RIPK3, ZBP1, in the upregulation of inlflammatory genes in these mice.
Publication Title
FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profile of squamous lung cancer cells are used to identify genes that are differentially regulated.
Publication Title
Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In inflammatory diseases of the airway, a high level (estimated to be as high as 8 mM) of HOCl can be generated through a reaction catalyzed by the leukocyte granule enzyme myeloperoxidase (MPO). HOCl, a potent oxidative agent, causes extensive tissue injury through its reaction with various cellular substances, including thiols, nucleotides, and amines. In addition to its physiological source, HOCl can also be generated by chlorine gas inhalation from an accident or a potential terrorist attack. Despite the important role of HOCl-induced airway epithelial injury, the underlying molecular mechanism is largely unknown. In the present study, we found that HOCl induced dose-dependent toxicity in airway epithelial cells. By transcription profiling using GeneChip, we identified a battery of HOCl-inducible antioxidant genes, all of which have been reported previously to be regulated by nuclear factor erythroid-related factor 2 (Nrf2), a transcription factor that is critical to the lung antioxidant response. Consistent with this finding, Nrf2 was found to be activated time and dose dependently by HOCl. Although the epidermal growth factor receptor-MAPK pathway was also highly activated by HOCl, it was not involved in Nrf2 activation and Nrf2-dependent gene expression. Instead, HOCl-induced cellular oxidative stress appeared to lead directly to Nrf2 activation. To further understand the functional significance of Nrf2 activation, small interference RNA was used to knock down Nrf2 level by targeting Nrf2 or enhance nuclear accumulation of Nrf2 by targeting its endogenous inhibitor Keap1. By both methods, we conclude that Nrf2 directly protects airway epithelial cells from HOCl-induced toxicity.
Publication Title
Identification of Nrf2-dependent airway epithelial adaptive response to proinflammatory oxidant-hypochlorous acid challenge by transcription profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
IlluminaHiSeq2000
Description
miRNA-1343 is an uncharacterized miRNA predicted to target a number of genes involved in epithelial cell function including TGF-beta signaling, cell adhesion, and cell proliferation. We transiently overexpressed miRNA-1343 or a non-targeting control miRNA in A549 and 16HBE14o- human airway cell lines. As predicted, RNA-seq following miRNA-1343 overexpression showed significant downregulation of genes involved in these pathways. Furthermore, genes involved in cholesterol and lipid biosynthesis were found to be significantly upregulated by miRNA-1343 overexpression. Overall design: mRNA profiles from A549 and 16HBE14o- cells transiently transfected with miRNA-1343 or a negative control (NC) miRNA, in quintuplicate.
Publication Title
miR-1343 attenuates pathways of fibrosis by targeting the TGF-β receptors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
PAX3-FOXO1 is a fusion transcription factor characteristic for the majority of alveolar rhabdomyosarcoma tumors. It is the main oncogenic driver and deregulates expression of PAX3 target genes.
Publication Title
Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Neuroprotective effects of NDP-MSH. We have characterized the signaling down-stream of melanocortin-1 receptor ligation to identify pathways mediating neuroprotective effects of NDP-MSH using transcriptional profiling. In this data set we included the expression data obtained from mouse brain tissue (MOG-immunized wild-type or C57BL/6Je/e mice at disease maximum, d14 after immunization). The data were used to obtain differentially regulated genes in wild-type or C57BL/6Je/e mice upon systemic NDP-MSH treatment.
Publication Title
Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human prostate cancer tissues analyses
Publication Title
In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples