Adverse prognosis of glioblastoma contacting the subventricular zone: biological correlates
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PROVIDER: PRJNA556417 | ENA |
REPOSITORIES: ENA
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2019-07-25 | GSE134783 | GEO
Project description:Introduction: The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma.Methods: We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary glioblastoma patients diagnosed between 2005-2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors. Protein expression patterns of a.o. markers of neural stem cellness (CD133 and GFAP-?) and (epithelial-) mesenchymal transition (NF-?B, C/EBP-? and STAT3) were determined with immunohistochemistry on tissue microarrays containing 220 of the tumors. Molecular classification and mRNA expression-based gene set enrichment analyses, miRNA expression and SNP copy number analyses were performed on fresh frozen tissue obtained from 76 tumors. Confirmatory analyses were performed on glioblastoma TCGA/TCIA data.Results: Involvement of the SVZ was a significant adverse prognostic factor in glioblastoma, independent of age, KPS, surgery type and postoperative treatment. Tumor volume and postoperative complications did not explain this prognostic effect. SVZ contact was associated with increased nuclear expression of the (epithelial-) mesenchymal transition markers C/EBP-? and phospho-STAT3. SVZ contact was not associated with molecular subtype, distinct gene expression patterns, or markers of stem cellness. Our main findings were confirmed in a cohort of 229 TCGA/TCIA glioblastomas.Conclusion: In conclusion, involvement of the SVZ is an independent prognostic factor in glioblastoma, and associates with increased expression of key markers of (epithelial-) mesenchymal transformation, but does not correlate with stem cellness, molecular subtype, or specific (mi)RNA expression patterns.
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Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors.
2013-09-09 | GSE47486 | GEO
Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors. Two-condition experiment, healthy vs. EAE derived SVZ progenitors. Biological replicates: 2 control replicates, 2 EAE replicates. SVZ progenitors were sorted in two cell populations: neuronal progenitors (PSA-NCAM magnetic sorting) and glial progenitors (NG2 magnetic sorting). Progenitors from healthy mice are reference samples.
2013-09-09 | E-GEOD-47486 | biostudies-arrayexpress
Project description:Metaphase karyotyping is an established diagnostic standard in acute myeloid leukemia (AML) for risk stratification. One of the cytogenetic findings in AML are structurally highly abnormal marker chromosomes. In this study, we have assessed frequency, cytogenetic characteristics, prognostic impact and underlying biological origin of marker chromosomes. Given their inherent gross structural chromosomal damage, we speculated that they may arise from chromothripsis, a recently described phenomenon of chromosome fragmentation in a single catastrophic event. In 2 large consecutive prospective, randomized, multicenter, intensive chemotherapy trials (AML96, AML2003) from the Study Alliance Leukemia (SAL), marker chromosomes were detectable in 165/1026 (16.1%) of aberrant non-core-binding-factor (CBF) karyotype patients. Adverse-risk karyotypes displayed a higher frequency of marker chromosomes (26.5% in adverse-risk, 40.3% in complex aberrant and 41.2% in abnormality(17p) karyotypes, p<.0001 each). Marker chromosomes were associated with a poorer prognosis compared to other non-CBF aberrant karyotypes and led to lower remission rates (CR+CRi), inferior event-free survival as well as overall survival in both trials. In multivariate analysis, marker chromosomes independently predicted poor prognosis in the AML96 trial ≤60 years. As detected by array-CGH, about one third of marker chromosomes (18/49) had arisen from chromothripsis, whereas this phenomenon was virtually undetectable in a control group of marker chromosome-negative complex aberrant karyotypes (1/34). The chromothripsis-positive cases were characterized by a particularly high degree of karyotype complexity and dismal prognosis. In conclusion, marker chromosomes are indicative of chromothripsis and associated with poor prognosis per se and not merely by association with other adverse cytogenetic features.
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Project description:Transforming growth factor (TGF)-ß1 is a multifunctional cytokine regulating a number of physiological and patho-physiological processes in the adult brain. Its expression is elevated during neurodegeneration, which is associated with reduced levels of neurogenesis. We have postulated that TGF-ß1 might be one of the crucial factors involved in limiting neurogenesis in the diseased brain. We used microarrays to detail the gene expression profile after TGFbeta-1 treatment and identified distinct classes of up- and downregulated genes. Keywords: control versus TGFbeta1 treated group Adult rat subventricular zone cells were cultured for 7 days under proliferation conditions. Control cells were exposed to HCl/BSA whereas TGFbeta-1 treated cells received 10 ng/ml TGFbeta-1 dissolved in HCl/BSA 3 times per week. RNA was extracted followed by hybridization on Affymetrix microarrays.
2011-05-10 | E-GEOD-14556 | biostudies-arrayexpress
Project description:Transforming growth factor (TGF)-ß1 is a multifunctional cytokine regulating a number of physiological and patho-physiological processes in the adult brain. Its expression is elevated during neurodegeneration, which is associated with reduced levels of neurogenesis. We have postulated that TGF-ß1 might be one of the crucial factors involved in limiting neurogenesis in the diseased brain. We used microarrays to detail the gene expression profile after TGFbeta-1 treatment and identified distinct classes of up- and downregulated genes. Keywords: control versus TGFbeta1 treated group Adult rat subventricular zone cells were cultured for 7 days under proliferation conditions. Control cells were exposed to HCl/BSA whereas TGFbeta-1 treated cells received 10 ng/ml TGFbeta-1 dissolved in HCl/BSA 3 times per week. RNA was extracted followed by hybridization on Affymetrix microarrays.
2011-05-10 | E-GEOD-14562 | biostudies-arrayexpress
Project description:Partial reprogramming has the potential to reverse age-related decline in some tissues. Its impact on the cell types within the aging brain, particularly the subventricular zone neurogenic niche, is unknown.
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Project description:Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts. Microarrays of neural stem cells, early progenitors and the tissue from subregions of the subventricular zone were compiled to screen for the full extent of heterogeneity in this region during postnatal life. Spatially distinct regions of the developing forebrain subventricular zone (SVZ) aged at P4, P8 and P11 were microdissected in RNAse free/sterile conditions. Mice expressing Ascl1-EGFP in the SVZ were used to aid accurate microdissection of the dorsal and lateral wall of each of the studied time points as per our previous publications characterizing this method. As well as at the whole microdomain level, additionally, NSCs (Hes5-EGFP+/Prom1+) and early progenitors (Ascl1-EGFP+) from each microdomain were further isolated by FAC sorting methods. This was to provide a comprehensive gene expression analysis at the tissue level and at the cellular level. Generally, 1 litter was used to yield 1 'n' number of replicates. A total of 23 affymetrix analysis were performed.
2015-04-07 | E-GEOD-60905 | biostudies-arrayexpress
Project description:Single cell RNA sequencing of mouse subventricular zone (SVZ) harboring a CGD1 transgene expressing GFP.
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