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GSE7824
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using Affymetrix HG-U133-Plus 2.0 array and Laser Capture Microdissection techniques, we determined whether growth in different zones of the same tumor affected expression of genes by human pancreatic cancer cells. Human L3.6pl pancreatic cancer cells were implanted into the pancreas of nude mice. Gene expression patterns in tumor cells within the central and peripheral zones were compared and statistical differences were determined for 1222 genes. Bioinformatic functional prediction analysis revealed that 346 upregulated genes in the peripheral zone were related to cytoskeleton organization and biogenesis, cell cycle, cell adhesion, cell motility, DNA replication, localization, integrin-mediated signaling pathway, development, morphogenesis, and IkB kinase/NF-kB cascade; and 876 upregulated genes in the central zone were related with regulation of cell proliferation, regulation of transcription, transmembrane receptor protein tyrosine kinase signaling pathway, response to stress, small GTPase mediated signal transduction, hexose metabolism, cell death, response to external stimulus, carbohydrate metabolism, and response to wounding. Results from the microarray were confirmed for reliability by in situ hybridization analysis. Collectively, these data demonstrate zonal heterogeneity for gene expression profiles in tumors and suggest that characterization of zonal gene expression profiles are essential to obtain reproducible data, to predict disease prognosis, and to design specific therapeutics.
Publication Title
Zonal heterogeneity for gene expression in human pancreatic carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DNA hypomethylation is an important epigenetic modification found to occur in many different cancer types, leading to the upregulation of previously silenced genes and loss of genomic stability. We previously demonstrated that hypoxia and hypoglycaemia (ischemia), two common micro-environmental changes in solid tumors, decrease DNA methylation through the downregulation of DNMTs in human colorectal cancer cells. Here, we utilized a genome-wide cross-platform approach to identify genes hypomethylated and upregulated by ischemia. Following exposure to hypoxia or hypoglycaemia, methylated DNA from human colorectal cancer cells (HCT116) was immunoprecipitated and analysed with an Affymetrix promoter array. Additionally, RNA was isolated and analysed in parallel with an Affymetrix expression array. Ingenuity pathway analysis software revealed that a significant proportion of the genes hypomethylated and upregulated were involved in cellular movement, including PLAUR and CYR61. A Matrigel invasion assay revealed that indeed HCT116 cells grown in hypoxic or hypoglycaemic conditions have increased mobility capabilities. Confirmation of upregulated expression of cellular movement genes was performed with qPCR. The correlation between ischemia and metastasis is well established in cancer progression, but the molecular mechanisms responsible for this common observation have not been clearly identified. Our novel results suggest that hypoxia and hypoglycaemia may be driving changes in DNA methylation through downregulation of DNMTs. This is the first report to our knowledge that provides an explanation for the increased metastatic potential seen in ischemic cells; i.e. that ischemia could be driving DNA hypomethylation and increasing expression of cellular movement genes.
Publication Title
Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The requirement of frozen tissues for microarray experiments limits the clinical usage of genome-wide expression profiling using microarray technology.
Publication Title
Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We have replaced the right arm of chromosome IX in Saccharomyces cerevisiae with a synthetic version to generate synIXR haploids. The synthetic chromosome features multiple sequeunce modifications.
Publication Title
Synthetic chromosome arms function in yeast and generate phenotypic diversity by design.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 118 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Despite continual efforts to rationalize a prognostic stratification of patients with esophageal adenocarcinoma (EAC) before treatment, current staging system only shows limited success owing to the lack of molecular and genetic markers that reflect prognostic features of the tumor. To develop molecular predictors of prognosis, we used systems-level characterization of tumor transcriptome. Using DNA microarray, genome-wide gene expression profiling was performed on 75 biopsy samples from patients with untreated EAC. Various statistical and informatical methods were applied to gene expression data to identify potential biomarkers associated with prognosis. Potential marker genes were validated in an independent cohort using quantitiative RT-PCR to measure gene expression. Distinct subgroups of EAC were uncovered by systems-level characterization of tumor transcriptome. We also identified a six-gene expression signature that could be used to predict overall survival (OS) of EAC patients. In particular, expression of SPARC and SPP1 was a strong independent predictor of OS, and a combined gene expression signature with these two genes was associated with prognosis (P < 0.024), even when all relevant pathological variables were considered together in multivariate Cox hazard regression analysis. Our findings suggest that molecular features reflected in gene expression signatures may dictate the prognosis of EAC patients, and these gene expression signatures can be used to predict the likelihood of prognosis at the time of diagnosis and before treatment.
Publication Title
Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 226 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before.
Publication Title
Transcriptomic architecture of the adjacent airway field cancerization in non-small cell lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the effect on global gene regulation in epididymal adipose tissue of overexpressing the cytoskeletal tropomyosin, Tm5NM1 to help understand the transcriptional events that lead to increased fat mass in transgenic mice.
Publication Title
Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 391 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression alterations in response to cigarette smoke have been characterized in normal-appearing bronchial epithelium of healthy smokers and it has been suggested that adjacent histologically normal tissue display tumor-associated molecular abnormalities.
Publication Title
Characterizing the molecular spatial and temporal field of injury in early-stage smoker non-small cell lung cancer patients after definitive surgery by expression profiling.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 22 Downloadable Samples
IlluminaHiSeq2500
Description
Estrogen receptor-a (ERa) is an important driver of breast cancer and is the target for hormonal therapies, anti-estrogens and drugs that limit estrogen biosynthesis (aromatase inhibitors). Mutations in the ESR1 gene identified in metastatic breast cancer provide a potential mechanism for acquired resistance to hormone therapies. We have used CRISPR-Cas9 mediated genome editing in the MCF-7 breast cancer cell line, generating MCF-7-Y537S. MCF-7-Y537S cells encode a wild-type (tyrosine 537) and a mutant (serine 537) allele. Growth of the line is estrogen-independent and expression of ERa target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ERa binding sites in the presence and absence of estrogen. RNA-seq following estrogen treatment was used for gene expression analysis. We show that expression of ER target genes and ER recruitment to ER binding regions is similar in MCF-7 and MCF-7-Y537S cells, except that ER recruitment to DNA and expression of ER target genes is frequently elevated in the absence of estrogen. Overall design: Hormone depleted MCF7 Luc or Y537S cells were treated with 10nM E2 or ethanol, as vehicle control, for 8 hours, with 3 replicates (2 replicates for Y537S + E2). RNA-seq was carried out using Illumina Hiseq 2500.
Publication Title
Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer.
Sample Metadata Fields
No sample metadata fields
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