Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883006 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR21778038_1.fastq.gz | Fastqsanger.gz | |||
| SRR21778038_2.fastq.gz | Fastqsanger.gz | |||
| SRR21778040_1.fastq.gz | Fastqsanger.gz | |||
| SRR21778040_2.fastq.gz | Fastqsanger.gz |
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Project description:High-grade gliomas are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type high-grade glioma (glioblastoma, GBM), increased intra-tumoral heterogeneity is associated with more aggressive disease. Recently, spatial technologies have emerged to dissect this complex heterogeneity within the tumor ecosystem by preserving cellular organization in situ. Here, we construct a high- resolution molecular landscape of GBM and IDH-mutant high-grade glioma patient samples to investigate the cellular subtypes and spatial communities that compose high-grade glioma using digital spatial profiling and spatial molecular imaging. This uncovered striking diversity of the tumor and immune microenvironment, that is embodied by the heterogeneity of the inferred copy- number alterations in the tumor. Reconstructing the tumor architecture revealed brain-intrinsic niches, composed of tumor cells reflecting brain cell types and microglia; and brain-extrinsic niches, populated by mesenchymal tumor cells and monocytes. We further reveal that cellular communication in these niches is underpinned by specific ligand-receptor pairs. This primary study reveals high levels of intra-tumoral heterogeneity in high-grade gliomas, associated with a diverse immune landscape within spatially localized regions.
2023-12-13 | GSE232469 | GEO
Project description:Background: Molecular profiling of diffuse gliomas has provided significant insights into the pathogenesis, classification and prognostication of these malignancies. However, previous molecular studies of glioma have largely focused on genomic readouts and targeted proteomic profiling technologies. Consequently, proteomic and downstream functional landscape of gliomas in general, and molecular subgroups in particular, remains largely unexplored. Here, we utilize liquid chromatography tandem mass spectrometry to profile genomically-defined cohorts of gliomas spanning the full range of World Health Organization (WHO) grades. Methods: Bulk frozen tissue and purified micro-dissected regions from formalin-fixed paraffin-embedded (FFPE) tissues were assembled and utilized to define robust proteomic signatures of both low grade, infiltrative and high-grade tumors. As a final analysis, primary tumor tissue was compared with both IDH-mutated and IDH-wildtype glioblastoma stem cell (GSC) lines to further overcome tissue heterogeneity and pinpoint proteins differences likely arising in the relevant glial cellular drivers of tumor development. Results: In aggregate, 5,496 unique proteins over 3 glioma cohorts were identified, and span common molecular subclasses based on IDH and 1p19q co-deletion status and all four WHO grades. Supervised clustering highlights substantial proteome and systems-level pathway differences between different genetically defined glioma subtypes and WHO grades. By using bulk tumor statistical analysis, 833 proteins distinguish different WHO grade tumors, while FFPE tumor dissection reveals 287 proteins in GBMs with abundance changes according to IDH mutation status. Using our integrative approach, calcium signaling, proteins of the endoplasmic reticulum and extracellular integrin proteins are most conserved proteomic markers that distinguish aggressive, IDH-wt, from IDH-mut GBM tumors in primary and tissue culture models gliomagenesis. Conclusions: This proteomic survey provides the largest and most diverse unbiased protein-based brain tumor resource to date. Current treatments for glial tumors are largely non-specific and overlap between genomic subtypes and WHO grades. Our analysis provides early insight into the vast downstream and epigenetic protein-level differences within this molecular framework. Given the central position proteins occupy in driving biology and phenotype, further characterization of the substantial proteomic diversity that exist between the molecular subtypes and grades of gliomas, proteomics may help define more personalized prognostic and predictive biomarkers for precision care.
2019-07-30 | PXD010099 | Pride
Project description:Background: Molecular profiling of diffuse gliomas has provided significant insights into the pathogenesis, classification and prognostication of these malignancies. However, previous molecular studies of glioma have largely focused on genomic readouts and targeted proteomic profiling technologies. Consequently, proteomic and downstream functional landscape of gliomas in general, and molecular subgroups in particular, remains largely unexplored. Here, we utilize liquid chromatography tandem mass spectrometry to profile genomically-defined cohorts of gliomas spanning the full range of World Health Organization (WHO) grades. Methods: Bulk frozen tissue and purified micro-dissected regions from formalin-fixed paraffin-embedded (FFPE) tissues were assembled and utilized to define robust proteomic signatures of both low grade, infiltrative and high-grade tumors. As a final analysis, primary tumor tissue was compared with both IDH-mutated and IDH-wildtype glioblastoma stem cell (GSC) lines to further overcome tissue heterogeneity and pinpoint proteins differences likely arising in the relevant glial cellular drivers of tumor development. Results: In aggregate, 5,496 unique proteins over 3 glioma cohorts were identified, and span common molecular subclasses based on IDH and 1p19q co-deletion status and all four WHO grades. Supervised clustering highlights substantial proteome and systems-level pathway differences between different genetically defined glioma subtypes and WHO grades. By using bulk tumor statistical analysis, 833 proteins distinguish different WHO grade tumors, while FFPE tumor dissection reveals 287 proteins in GBMs with abundance changes according to IDH mutation status. Using our integrative approach, calcium signaling, proteins of the endoplasmic reticulum and extracellular integrin proteins are most conserved proteomic markers that distinguish aggressive, IDH-wt, from IDH-mut GBM tumors in primary and tissue culture models gliomagenesis. Conclusions: This proteomic survey provides the largest and most diverse unbiased protein-based brain tumor resource to date. Current treatments for glial tumors are largely non-specific and overlap between genomic subtypes and WHO grades. Our analysis provides early insight into the vast downstream and epigenetic protein-level differences within this molecular framework. Given the central position proteins occupy in driving biology and phenotype, further characterization of the substantial proteomic diversity that exist between the molecular subtypes and grades of gliomas, proteomics may help define more personalized prognostic and predictive biomarkers for precision care.
2019-07-30 | PXD010098 | Pride
Project description:Background: Molecular profiling of diffuse gliomas has provided significant insights into the pathogenesis, classification and prognostication of these malignancies. However, previous molecular studies of glioma have largely focused on genomic readouts and targeted proteomic profiling technologies. Consequently, proteomic and downstream functional landscape of gliomas in general, and molecular subgroups in particular, remains largely unexplored. Here, we utilize liquid chromatography tandem mass spectrometry to profile genomically-defined cohorts of gliomas spanning the full range of World Health Organization (WHO) grades. Methods: Bulk frozen tissue and purified micro-dissected regions from formalin-fixed paraffin-embedded (FFPE) tissues were assembled and utilized to define robust proteomic signatures of both low grade, infiltrative and high-grade tumors. As a final analysis, primary tumor tissue was compared with both IDH-mutated and IDH-wildtype glioblastoma stem cell (GSC) lines to further overcome tissue heterogeneity and pinpoint proteins differences likely arising in the relevant glial cellular drivers of tumor development. Results: In aggregate, 5,496 unique proteins over 3 glioma cohorts were identified, and span common molecular subclasses based on IDH and 1p19q co-deletion status and all four WHO grades. Supervised clustering highlights substantial proteome and systems-level pathway differences between different genetically defined glioma subtypes and WHO grades. By using bulk tumor statistical analysis, 833 proteins distinguish different WHO grade tumors, while FFPE tumor dissection reveals 287 proteins in GBMs with abundance changes according to IDH mutation status. Using our integrative approach, calcium signaling, proteins of the endoplasmic reticulum and extracellular integrin proteins are most conserved proteomic markers that distinguish aggressive, IDH-wt, from IDH-mut GBM tumors in primary and tissue culture models gliomagenesis. Conclusions: This proteomic survey provides the largest and most diverse unbiased protein-based brain tumor resource to date. Current treatments for glial tumors are largely non-specific and overlap between genomic subtypes and WHO grades. Our analysis provides early insight into the vast downstream and epigenetic protein-level differences within this molecular framework. Given the central position proteins occupy in driving biology and phenotype, further characterization of the substantial proteomic diversity that exist between the molecular subtypes and grades of gliomas, proteomics may help define more personalized prognostic and predictive biomarkers for precision care.
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Project description:Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage. 80 tumor samples, one normal tissue sample (brain)
2012-02-24 | E-GEOD-35158 | biostudies-arrayexpress
Project description:Gliomas are an incurable malignancy of the central nervous system. Patients that present with this disease have poor prognosis, necessitating the development of new therapeutic approaches. Glioblastoma is the most aggressive form of the disease and although lower grade gliomas have an intially better prognosis, they often progress to high grade glioma. Immunotherapy has been successful in other solid malignancies, but has not demonstrated efficacy in gliomas. Isocitrate dehydrogenase (IDH) is mutated in the majority of lower grade gliomas, and differences in the microenvironment between IDHmut and IDHwt disease contribute to differences in antitumor immunity. However, it remains unknown whether there are similiarites or differences between the immune landscape of IDHmut versus IDHwt gliomas. To address this question, we generated single-cell RNAseq data from 19 patients with grade II-IV glioma, of which 13 were IDHwt and 6 were IDHmut.
2025-08-04 | GSE247824 | GEO
Project description:Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage.
2012-02-24 | GSE35158 | GEO
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Project description:B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, the function beyond immune regulation of B7H3 has been widely studied. However, the expression preference and the regulation mechanism underlying B7H3 in different subtypes of gliomas is rarely understood. We show here that B7H3 expression is significantly decreased in IDH-mutated gliomas and in cultured IDH1-R132H glioma cells. Accumulation of 2-HG leads to a remarkable downregulation of B7H3 protein and the activity of IDH1-R132H mutant is responsible for B7H3 reduction in glioma cells. Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells. In the meantime, the autophagy flux is more active with higher LC3B-II and lower p62 in IDH1-R132H glioma cells than in IDH1-WT cells. Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs 'F-V-S/N-I/V' in B7H3. Moreover, B7H3 interacts with p62 and CQ treatment significantly enhances this interaction. Additionally, we find that <i>B7H3</i> is positively correlated with <i>VEGFA</i> and <i>MMP2</i> by bioinformatics analysis in gliomas. B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HG<sup>high</sup> gliomas compared to 2-HG<sup>low</sup> glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.
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Project description:Immune and tumor cell landscape in pediatric high grade gliomas
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