GBM invasion transcriptiome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12689 | GEO | 2008/10/19
SECONDARY ACCESSION(S): PRJNA112695
REPOSITORIES: GEO
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Project description:Glioblastoma multiforme (GBM), the most advanced form of a large subset of brain tumors collectively known as glioma, is the most aggressive and invasive type of brain tumor. Patients usually experience a median survival range of 9 to 12 months. GBMs are extremely difficult to manage because of the tumor cellsâ tendency to migrate and pervade into adjacent tissues. Surgical resection of GBMs generally only slows disease progression because any remaining tumor cells proceed to migrate through brain tissues and reform a new tumor mass. It is hypothesized that the invasive phenotype of these tumor cells may be attributable to unique gene expression. Stationary core and invasive rim tumor cells were collected separately by laser capture microdissection (LCM) from 19 biopsy samples. Identification of differentially expressed genes in the tumor core and invasive rim can give valuable insight to the genes and pathways potentially involved with the invasive phenotype. This information can then be used to generate possible biomarkers, diagnostic markers, or drug targets. Human glioblastoma tumor samples were obtained from patients who underwent primary therapeutic brain tumor resection. All specimens were collected and submitted to the study under institutional review board approved protocols. None of the patients had been subjected to chemotherapy or radiotherapy prior to resection, in order to avoid genetic signatures that are due to exposure to alkylating agents and/or ionizing radiation. All specimens were verified as GBMs by a neuropathologist. Tumors are embedded in OCT, then sectioned in a cryostat at -20C, to a thickness of 8-10 um and placed onto HistoGene slides. Sections to be microdissected are removed from the -80C fixed and stained with an abbreviated Hematoxylin and Eosin protocol. Two thousand tumor core and invasive cells are dissected onto separate caps using the PixCell II instrument using CapSure⢠Macro LCM Caps. The CapSure⢠Macro LCM Caps LCM 0211 should be used with the AutoPix instrument. Cells in the tumor core are identified by nuclear atypia and size and captured using the larger spot sizes. Tumor cells immediately adjacent to necrotic areas, cortical areas, cells with small regular nuclei, endothelial and blood cells should be avoided. Individual white matter invading GBM cells can be identified by means of their nuclear atypia and heteropyknotic staining, which is consistent with that of the cells within the tumor core. They should be microdissected using the 7.5 um laser spot size and the initial power settings recommended by the PixCell II manual. After microdissection all harvested material should immediately be lysed on the cap by applying the lysis buffer (XB) from the PicoPure RNA Isolation Kit according to the PicoPure protocol and stored -80C. Cell populations harvested on different caps can be pooled at the time of RNA isolation. RNA integrity is varified by identification of distinct 28S and 18S ribosomal bands with an Agilent Bioanalyzer using the RNA 6000 Nano LabChip kit. Total RNA was isolated from 2000 LCM cells (to ensure at least 500 ng total RNA) using the PicoPure RNA solation Kit, following manufacturers protocol. mRNA is reverse transcribed with the RiboAmp RNA Amplification kit. 500 ng total RNA is amplified with the RiboAmp RNA Amplification kit, following manufacturerâs instructions. The total yield that can be expected falls between 30 and 60 µg copy RNA. The size of the copy RNA should be verified by gel electrophoresis. Approximately 500ng of copy RNA can be separated on a 1% agarose gel in TAE buffer. A smear of amplified material should be seen between 200 and 3000bp. Six µg amplified RNA are labeled in a RT with SuperScriptIII in the presence of dUTP Cy5 utilizing 6 µg random hexamers as primers. Universal reference RNA is amplified one round in the same manner and labeled with Cy3 dUTP. Labeled cDNA is hybridized overnight onto cDNA microarray. Following hybridization, arrays are washed, scanned and quantitated with the Axon GenePix 4000 microarray reader (Axon Instruments). Gene expression results are analyzed using GeneSpring (Silicon Genetics) software. Intensity dependent normalization is applied, where the ratio is reduced to the residual Lowess fit of the intensity versus ratio curve. The measured intensity of each gene is divided by its reference channel (signal from the universal reference RNA) in each sample. When the reference channel is below 10, the data point is considered uninformative. The ratios (sample over reference) for the tumor core experiments and invasive rim experiments are averaged and compared. Genes that are more than two-fold differentially regulated in the majority of the matched core/invasive rim sets are selected.
2010-05-18 | E-GEOD-12689 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells.
2005-11-11 | E-SMDB-2677 | biostudies-arrayexpress
Project description:<p>Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs).</p><p>Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker.</p><p>Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.</p><p><br></p><p><strong>Stem cell and cell line assays</strong> are reported in the current study <strong>MTBLS4708</strong></p><p><strong>Xenograft assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS730' rel='noopener noreferrer' target='_blank'><strong>MTBLS730</strong></a></p>
2022-11-08 | MTBLS4708 | MetaboLights
Project description:<p>Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs).</p><p>Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker.</p><p>Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.</p><p><br></p><p><strong>Xenograft assays</strong> are reported in the current study <strong>MTBLS730</strong></p><p><strong>Stem cell and cell line assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4708' rel='noopener noreferrer' target='_blank'><strong>MTBLS4708</strong></a></p>
2022-11-08 | MTBLS730 | MetaboLights
Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Using regression correlation
2006-01-18 | E-GEOD-4058 | biostudies-arrayexpress
Project description:Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs). Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker. Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.
2022-11-08 | GSE202200 | GEO
Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2006-01-19 | GSE4058 | GEO
Project description:Medulloblastomas (MBs) and Glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with onset and progression. Here, we describe differences between the ECM signature of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples among each other and their normal decellularized brain site counterparts. Our analysis reveals that 19 proteins were differentially expressed in MBs, 28 proteins in GBMs, and 11 proteins in both MBs and GBMs. Next, we validated key findings by protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from microarray-GSE50161, and 115 GBM samples from RNAseq-TCGA. We report a shift towards a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology.
2021-12-30 | PXD023350 | Pride
Project description:RNAseq of Human Glioblastoma with samples from core, rim and invasive (isolated based on 5ALA) tumour areas
| PRJEB36495 | ENA
Project description:Glioblastomas (GBM) are the most aggressive type of brain tumors with a dismal prognosis. The effectiveness of anti-tumor drugs is thwarted by brain endothelial cells (ECs) in the tumor microenvironment. However, the characteristics of ECs remains poorly inventoried at the single-cell level. We performed single-cell RNA sequencing (scRNA-seq) for ECs from 4 GBMs and matching non-malignant brain samples, and identified distinct EC phenotypes in GBM.
2021-07-08 | GSE162631 | GEO