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GSE85570
Homo sapiens
437 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate -H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual -H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed 2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of -H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer
Publication Title
Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
During neurogenesis, expression of the basic Helix-Loop-Helix NeuroD6/Nex1/MATH-2 transcription factor parallels neuronal differentiation, while maintaining the differentiated state in the mature nervous system. To further dissect NeuroD6 differentiation properties, we previously generated a NeuroD6-overexpressing stable PC12 cell line, PC12-ND6, which displays a neuronal phenotype characterized by spontaneous neuritogenesis, accelerated NGF-induced differentiation, and increased regenerative capacity. Furthermore, we reported that NeuroD6 promotes long-term neuronal survival upon oxidative stress triggered by serum deprivation. In this study, we identified the NeuroD6-mediated transcriptional regulatory pathways linking neuronal differentiation to survival, by conducting a genome-wide microarray analysis using PC12-ND6 cells and serum deprivation as a stress paradigm. Through a series of filtering steps and a gene-ontology analysis, we found that NeuroD6 promotes distinct but overlapping gene networks, consistent with the differentiation, regeneration, and survival properties of PC12-ND6 cells. Using a gene set enrichment analysis, we provide the first evidence of a compelling link between NeuroD6 and a set of heat shock proteins in the absence of stress, which may be instrumental to confer stress tolerance to PC12-ND6 cells. Immunocytochemistry results showed that HSP27 and HSP70 interact with cytoskeletal elements, consistent with their roles in neuritogenesis and preserving cellular integrity. HSP70 also colocalizes with mitochondria located in the soma, growing neurites and growth cones of PC12-ND6 cells prior to and upon stress stimulus, consistent with its neuroprotective functions. Collectively, our findings support the notion that NeuroD6 links neuronal differentiation to survival via the network of molecular chaperones and endows the cells with increased stress tolerance.
Publication Title
NeuroD6 genomic signature bridging neuronal differentiation to survival via the molecular chaperone network.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Comparison of human prepuberal articular and growth plate cartilage
Publication Title
Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 350 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 228 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
Samples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.
Publication Title
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 122 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Samples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.
Publication Title
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 229 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms.
Publication Title
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
Sample Metadata Fields
Specimen part
View Samples