Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human Cerebrospinal Fluid modulates pathways promoting Glioblastoma malignancy

ABSTRACT: Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF of cancer and non cancer origin to measure changes in gene expression profile associated with increased malignancy and their clinical relevance on disease outcome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161528 | GEO | 2020/11/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Human cerebrospinal fluid impacts chemo-radiotherapy sensitivities in tumour cells from glioblastoma patients

Project description:Cancers in the central nervous system resist therapies effective in other cancers, possibly due to the unique biochemistry of the human brain microenvironment comprised of cerebrospinal fluid (CSF). However, the impact of CSF on cancer cells and therapeutic efficacy is unknown. Here we examined the effect of human CSF on glioblastoma (GBM) tumours from 25 patients. We found that CSF induces tumour cell plasticity and resistance to standard GBM treatments (temozolomide and irradiation). We identified nuclear-protein-1 (NUPR1), a transcription factor hampering ferroptosis, as a mediator of therapeutic resistance in CSF. NUPR1 inhibition with a repurposed antipsychotic, trifluoperazine, enhanced the killing of GBM cells resistant to chemoradiation in CSF. The same chemo-effective doses of trifluoperazine were safe for human neurons and astrocytes derived from pluripotent stem cells. These findings reveal that chemoradiation efficacy decreases in human CSF and suggest that combining trifluoperazine with standard care may improve GBM patient survival.

2023-10-20 | GSE243501 | GEO

Genome-wide methylation analysis of cerebrospinal fluid circulating tumor DNA: a new biomarker for recurrent glioblastoma [MeDIP-Seq]

Project description:Background: Glioblastoma (GBM) is a common malignancy of the central nervous system (CNS) that is prone to recurrent and has a short survival period. Clinical biomarkers for the diagnosis and prognosis of recurrent GBM are lacking.Methods: We collected 4 cerebrospinal fluid (CSF) samples and 1 normal CSF sample from recurrent GBM, as well as paired tissue samples. Genome-wide methylation profiles of CSF circulating tumor DNA (ctDNA) and tissue mRNA transcription profiles were analyzed, and genes were screened by univariate Cox analysis, Lasso regression analysis, and multivariate Cox analysis by the Chinese Glioma Genome Atlas (CGGA) database. Data analysis and visualization were performed using R software, SPSS software, and Graphpad Prism.Results: By taking the intersection of differentially methylated regions (DMRs) and differentially expressed genes (DEGs), 892 genes were selected for Lasso regression analysis and multivariate Cox analysis, and 12 hub genes were finally screened to construct diagnostic and prognostic models. The diagnostic (AUC=0.982) and prognostic (5-years AUC=0.931) models based on the 12 hub genes had high accuracy.Conclusions: This study reveals that 12 hub genes in CSF ctDNA can diagnose and prognosticate recurrent GBM and provide new biomarkers for clinical research into the mechanisms of GBM recurrent.

2023-05-01 | GSE205513 | GEO

Genome-wide methylation analysis of cerebrospinal fluid circulating tumor DNA: a new biomarker for recurrent glioblastoma [mRNA-Seq]

2023-05-01 | GSE205512 | GEO

Gene Expression Analysis of Nestin-creERT2, or NG2-creERTM driven P53f/f; Nf1f/+; Ptenf/+ mouse GBM

Project description:We have developed spontaneous genetically engineered GBM mouse models from two distinct cells of origin: subventricular zone neural stem cells (SVZ; Nestin-creERT2) and oligodendrocyte lineage progenitor cells (OPC; NG2-creERTM). These tumors are biologically separable and are reflective of their lineage of origin.

2020-03-31 | GSE127273 | GEO

Cerebrospinal fluid cell-free DNA methylomes subtyping pediatric medulloblastoma

2023-06-01 | GSE178169 | GEO

Phosphoproteome Analysis of Cerebrospinal Fluid Extracellular Vesicles in Primary Central Nervous System Lymphoma

Project description:Primary central nervous system lymphoma(PCNSL) is a rare extra-nodal non-Hodgkin’s lymphoma and accounts for 3%-4% of central nervous system tumors. Recent studies have highlighted the importance of cerebrospinal fluid derived extracellular vesicles in PCNSL. Extracellular vesicles(EVs) are nanoscale vesicles with bilayer lipid membrane released by almost all cell types. EVs are present in body fluids, including urine, blood and CSF. Cerebrospinal fluid(CSF) is a colorless fluid that surrounds the brain and spinal cord and acts as lymph in the central nervous system. CSF-derived EVs contain proteins from neurons, oligodendrocytes, astrocytes and microglias. Studies of CSF EVs are mainly limited by the amount of EVs isolated from per milliliter of CSF and the volume of CSF acquired from one patient. Here, we provide a label-free quantitative phospho-proteome profiling of EVs separated from PCNSL and non-PCNSL CSF samples by an earlier introduced functional magnetic beads called EVTRAP together with highly sensitive timsTOF Pro.

2023-07-12 | PXD040744 | JPOST Repository

Reliable tumor detection using cerebrospinal fluid cell-free DNA methylomes in pediatric medulloblastoma

Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation and hydroxymethylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from 3 MB patients. We find highly concordance of DNA methylation and hydroxymethylation between CSF ctDNA and tumor DNA, especially in CpG islands. Importantly, CSF ctDNA can mostly recapitulate the dynamic changes of DNA methylation and hydroxymehtylation in tumor species compared to healthy cerebellums. Those MB tumor signature CpGs’ DNA methylation status are recovered in CSF ctDNA can clearly distinguish MB subgroups by utilizing public large cohort data. We further identified potential diagnostic and prognostic DNA methylation markers in CSF ctDNA. Our results show that CSF ctNDA methylation and hydroxymethylation can be a minimal invasive method to assess epigenetic alterations of MB, which is complementary to current diagnoses of MB tumors.

2020-10-28 | GSE142241 | GEO

Epigenetic regulation by chromatin activation mark H3K4me3 in primate progenitor cells within adult neurogenic niche [ChIP-seq]

Project description:Histone 3 lysine 4 trimethylation (H3K4me3) is known to be associated with transcriptionally active or poised genes and required for postnatal neurogenesis within the subventricular zone (SVZ) in the rodent model. Previous comparisons have shown significant correlation between baboon (Papio anubis) and human brain. In this study, we demonstrate that chromatin activation mark H3K4me3 is present in undifferentiated progenitor cells within the SVZ of adult baboon brain. To identify the targets and regulatory role of H3K4me3 within the baboon SVZ, we developed a technique to purify undifferentiated SVZ cells while preserving the endogenous nature without introducing culture artifact to maintain the in vivo chromatin state for genome-wide studies (ChIP-Seq and RNA-Seq). Overall, H3K4me3 is significantly enriched for genes involved in cell cycle, metabolism, protein synthesis, signaling pathways, and cancer mechanisms. Additionally, we found elevated levels of H3K4me3 in the MRI-classified SVZ-associated Glioblastoma Multiforme (GBM), which has a transcriptional profile that reflects the H3K4me3 modifications in the undifferentiated progenitor cells of the baboon SVZ. Our findings highlight the importance of H3K4me3 in coordinating distinct networks and pathways for life-long neurogenesis, and suggest that subtypes of GBM could occur, at least in part, due to aberrant H3K4me3 epigenetic regulation. SVZ H3K4me3 ChIP-seq profile of an adult baboon brain was generated by deep sequencing with Illumina HiSeq 2000.

2014-07-16 | E-GEOD-58530 | biostudies-arrayexpress

Single-cell RNA and TCR sequencing of IgG4-related disease cerebrospinal fluid

Project description:Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells in a variety of organs. Clinical presentation is heterogeneous and pathophysiological mechanisms of IgG4-related autoimmunity remain elusive. Secondary parenchymal lesions of IgG4-RD in the central nervous system (CNS) are rare and there are very few cases of IgG4-RD with isolated CNS manifestation. Patients suffering from IgG4-RD frequently require prolonged treatment with glucocorticoids and are often unable to taper these medications. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an unusual inflammatory intracranial pseudotumor we provide novel insights into the immuno-pathophysiology of IgG4-RD by illustrating an IgG4-RD-associated polyclonal T cell response in the CSF and multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells.

2021-06-19 | E-MTAB-10479 | biostudies-arrayexpress

Medulloblastoma cerebrospinal fluid reveals hypoxic indicators (metabolites and lipids) and cancer-specific RNAs

Project description:Medulloblastoma (MB) is the most common malignant brain tumor in children. There remains an unmet need for diagnostics to sensitively detect the disease, particularly recurrences. Cerebrospinal fluid (CSF) provides a window into the central nervous system, and liquid biopsy of CSF could provide a relatively non-invasive means for disease diagnosis. CSF samples from patients with or without medulloblastoma (MB) were subjected to RNA-sequencing to identify differentially expressed transcripts. Although the transcriptomic signatures in CSF to differentiate MB subgroup separation was challenging, we were able to identify a group of gene signatures that could separate cancer from normal CSF. Our approach provides several candidate signatures that deserve further validation, including the novel circular RNA circ_463, and insights into the impact of MB on the CSF microenvironment.

2022-03-04 | GSE189919 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data