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 SamplesPhosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesThe five DLBCL cell lines were treated with R406 to assess the signature of SYK inhibition. In previous studies, R406 decreased the proliferation and induced apoptosis of these surface Ig+ cell lines. In the previous studies, R406 inhibited the autophosphorylation of SYK 525/526 and SYK-dependent phosphorylation of BCR signaling components such as BLNK.
SYK inhibition modulates distinct PI3K/AKT- dependent survival pathways and cholesterol biosynthesis in diffuse large B cell lymphomas.
Specimen part, Cell line, Treatment, Time
View SamplesmRNA expression was assayed from bronchial epithelial cells collected via bronchoscopy and nasal epithelial cells collected by brushing the inferior turbinate from healthy current and never smoker volunteers in order to determine the relationship between smoking-related gene expression changes in bronchial and nasal epithelium within the same individual.
Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium.
Sex, Age, Specimen part, Race
View SamplesCytologically normal airway epithelial samples were collected during bronchoscopy of current and former smokers. Subjects enrolled in this study were either under suspicion of having lung cancer, had dysplasia in their airway, or were a healthy current, former or never smoker. We supplemented existing GEO series (GSE4115 and GSE7895) with the samples in this study to explore PI3K pathway activity in the these cohorts.
Airway PI3K pathway activation is an early and reversible event in lung cancer development.
No sample metadata fields
View SamplesBackground: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesPrimary mouse bone marrow mesenchymal stromal cells (BM-MSCs) cultured for bone differentiation were exposed to vehicle (DMSO), synthetic RXR ligand (LG100268), type 2 diabetes therapeutic and PPAR ligand (Rosiglitazone), and environmental PPAR ligands (Tributyltin, Triphenyl Phosphate, and MEHP) to evaluate differential gene expression as well as nuclear receptor expression and downstream PPARG target gene expression between all chemical exposures
Tributyltin induces a transcriptional response without a brite adipocyte signature in adipocyte models.
Sex, Specimen part
View SamplesExposure to indoor air pollution generated from the combustion of solid fuels is a major risk factor for a spectrum of cardiovascular and respiratory diseases, including lung cancer. In Chinas rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the country. While the elevated disease risk in this population has been linked to the widespread usage of bituminous (smoky) coal as compared to anthracite (smokeless) coal, the underlying physiologic mechanism that smoky coal induces in comparison to other fuel types is unclear. As we have previously used airway gene-expression profiling to gain molecular insights into the physiologic effects of cigarette smoke, here we profiled the buccal epithelium of residents exposed to the burning of smoky and smokeless coal in order to understand the physiologic effects of solid fuels.
Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.
Sex, Age, Specimen part
View SamplesVaccine adjuvants enhance the immune response to vaccines, resulting more robust and durable immune responses. Although extensive work has been done on the response to a single vaccination over time, here we seek to characterize the response over the course of multiple vaccinations.
No associated publication
Specimen part, Treatment, Time
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