We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelium gene expression is similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers with pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n=375) and AEGIS-2 (n=130) clinical trials and gene expression profiled using microarrays. Using the 375 AEGIS 1 samples, we identified 535 genes that were differentially expressed in the nasal epithelium of patients who were ultimately diagnosed with lung cancer vs. those with benign disease after one year of follow-up (p<0.001). Using bronchial gene expression data from 299 AEGIS-1 patients (including 157 patients with matched nasal and bronchial expression data), we found significantly concordant cancer-associated gene expression differences between the two airway sites (p<0.001). Differentially expressed genes were enriched for genes associated with the regulation of apoptosis, mitotic cell cycle, and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors and nasal gene expression had significantly higher AUC (0.80) and sensitivity (0.94) over a clinical-factor only model (p<0.05) in independent samples from the AEGIS-2 cohort (n=130). These results suggest that the airway epithelial field of lung cancer-associated injury in current and former smokers extends to the nose and demonstrates the potential of using nasal gene expression as a non-invasive biomarker for the detection of lung cancer.
Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.
Sex, Age
View SamplesBACKGROUND: In patients with suspicious pulmonary lesions, bronchoscopy is frequently non-diagnostic. This often results in additional invasive testing, including surgical biopsy, although many patients have benign disease. We sought to validate an airway gene-expression classifier for lung cancer in patients undergoing diagnostic bronchoscopy. METHODS: Two multicenter prospective studies (AEGIS 1 and 2) enrolled 1357 current or former smokers undergoing bronchoscopy for suspected lung cancer. Bronchial epithelial cells were collected from normal appearing mucosa in the mainstem bronchus during bronchoscopy. Patients without a definitive diagnosis from bronchoscopy were followed for 12 months. A gene-expression classifier was used to assess the risk of lung cancer, and its performance was evaluated. RESULTS: A total of 298 patients from AEGIS 1 and 341 from AEGIS 2 met criteria for analysis. Bronchoscopy was non-diagnostic for cancer in 272 of 639 patients (43%; 95%CI, 39-46%). The gene expression classifier correctly identified 431 of 487 patients with cancer (89% sensitivity; 95%CI, 85-91%), and 72 of 152 patients without cancer (47% specificity; 95%CI, 40-55%). The combination of the classifier and bronchoscopy had a sensitivity of 97% (95%CI, 95-98%), which was independent of size, location, stage, and histological subtype of lung cancer. In patients with an intermediate pre-test risk (10-60%) of lung cancer, the NPV of the classifier was 91% (95%CI 75-98%). CONCLUSIONS: In patients with an intermediate risk of lung cancer and a non-diagnostic bronchoscopy, a gene-expression classification of low-risk warrants consideration of a more conservative diagnostic approach that could reduce unnecessary invasive testing in patients with benign disease.
A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
Sex, Specimen part
View SamplesIn this study we aimed to assess technical variability associated with globin depletion in addition to assessing general technical variability in RNA-Seq from whole blood derived samples. We compared technical and biological replicates having undergone globin depletion or not and found that globin depletion removed approximately 80% of globin transcripts, improved the correlation of technical replicates, allowed for reliable detection of thousands of additional transcripts and generally increased transcript abundance measures. Overall design: Peripheral whole blood transcriptome assessed by RNA-Seq on Illumina HiSeq 2000 in 6 healthy individuals and 6 pooled samples, either globin depleted or not.
Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion.
No sample metadata fields
View SamplesThe goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Subject
View SamplesHalf of prostate cancers are caused by a gene-fusion that enables androgens to drive expression of the normally silent ETS transcription factor ERG in luminal prostate cells1-4. Recent prostate cancer genomic landscape studies5-10 have reported rare but recurrent point mutations in the ETS repressor ERF11. Here we show these ERF mutations cause decreased protein stability and ERF mutant tumours are mostly exclusive from those with ERG fusions. ERF loss recapitulates the morphologic and phenotypic features of ERG gain in primary mouse prostate tissue, including expansion of the androgen receptor (AR) transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of PTEN loss that yields oncogenic activity by ERG. Furthermore, in a human prostate cancer model of ERG gain and wild-type ERF, ChIP-seq studies indicate that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites. Consistent with a competition model, ERF loss rescues ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by displacement of ERF and raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors. Overall design: Murine Pten+/+ prostates were infected with shNT or shErf lentivirus, selected with antibiotics and 2 rounds of FACS. For each condition, 2 sets of equal numbers of cells were plated and then processed for RNA extraction and RNA-seq independently.
ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis.
Subject
View SamplesCD11c+ B cells (IgD+ and IgD-) are pathogenic B cells expanded in autoimmune disease. The purpose of this study is to identify the pathways unique to IgD+ CD11c B cells and IgD- CD11c B cells. Overall design: B cell subsets were isolated from peripheral blood and RNA sequencing was performed with Hiseq 2000 platform
IL-21 drives expansion and plasma cell differentiation of autoreactive CD11c<sup>hi</sup>T-bet<sup>+</sup> B cells in SLE.
Specimen part, Disease, Subject
View SamplesTranscript profiling and gene expression studies in NAE-treated seedlings: Seeds were germinated and seedlings maintained for 4 d in liquid MS media supplemented with 35 uM NAE(12:0)(N-lauroylethanolamine) prior to RNA isolation.
N-Acylethanolamine metabolism interacts with abscisic acid signaling in Arabidopsis thaliana seedlings.
Age, Specimen part, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesThe goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesGene expression analysis in control and diabetic rats. Diabetes-induced erectile dysfunction in rat model of DM. 10 weeks of streptozotocin induced diabetes. F344 Rats.
Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats.
No sample metadata fields
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