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.
A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma.
No sample metadata fields
View SamplesBarretts esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE.
Global changes in gene expression of Barrett's esophagus compared to normal squamous esophagus and gastric cardia tissues.
Specimen part
View SamplesTobacco 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.
Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.
Sex, Age
View SamplesHuman mononuclear cells were cultured in 2 phases. In the 1st phase the culture medium contained cyclosporine A the 2nd phase contained SCF and erythropoietin. Cells were collected at 3 stages of differentiation; on day 6, 10, 12 and represented early erythroblasts, medium stage and normoblasts.
Identification of gene networks associated with erythroid differentiation.
No sample metadata fields
View SamplesPrimary mielofibrosis (PMF) is a rare chronic myeloproliferative disorder characterized by the accumulation of abnormal megakaryocytes (Mks) in the bone marrow (BM), variable degrees of BM fibrosis, osteosclerosis and angiogenesis, immature myeloid and erythroid cells, and tear-drop erythrocytes in the peripheral blood (PB), and extramedullary hematopoiesis. The identification of the JAK2V617F mutation represented a seminal discovery in the field of Philadelphia-chromosomenegative chronic myeloproliferative neoplasms (MPNs), providing clues to the pathogenesis, prompting a revision of the diagnostic criteria, and culminating in the development of clinical trials with JAK2 (and JAK1) inhibitors. The JAK2V617F mutation occurs in almost all patients with polycythemia vera (PV) and in 50%-70% of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Soon after the identification of the JAK2V617F mutation, mutations in JAK2 exon 12 were described in rare patients with JAK2V617F-negative PV and mutations in MPL were reported in 5%-10% of ET or PMF subjects. The complexity of the molecular pathogenesis of MPNs is reinforced by discovery of additional mutations in TET2, ASXL1, CBL, IDH1/IDH2, EZH2 and IKZF1. These mutations are detected in a minority of patients at different phases of the disorder, including leukemic transformation, and are variably associated each other and with JAK2 or MPL mutations.
Mutations and prognosis in primary myelofibrosis.
Specimen part, Disease
View SamplesWe profiled the transcriptome of Drosophila melanogaster embryos in ttk2D50 embryos or after over-expression using btl-GAL4; UAS-ttk, respectively. We further isolated cells that express btl-enh-RFPmoe (Cabernard and Affolter 2005) and FACS sorting, and profiled their transcriptomes in the same genetic backgrounds.
Tramtrack is genetically upstream of genes controlling tracheal tube size in Drosophila.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with the deletion of a portion of the Alu element from MIR205HG transcript
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with MIR205HG knock-down in RWPE-1 cells
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
No sample metadata fields
View SamplesWe show that mesenchymal CSC-like cells express an embryonic stem cell signature that is mutant p53 dependent Overall design: Examination of three p53 mutant mesenchymal stem cells and ten derived CSC-like cell lines and 2 derived p53 mutant KO clones compared to control clones
A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells.
Specimen part, Cell line, Subject
View Samples