Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184472 | GEO | 2023/05/26
REPOSITORIES: GEO
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Project description:Glioblastoma (GBM) is the most aggressive form of brain cancer, characterized by high recurrence and dismal prognosis. Presently, there is no effective in vitro platform that can rapidly measure complex cellular phenotypic traits and predict patient-specific clinical outcomes. Here, we fabricated and evaluated an in vitro testing platform, Microfluidic Assay for Quantification of Cell Invasion (MAqCI), by screening a panel of 28 patient-derived primary GBM specimens in a blinded multi-institutional retrospective cohort study. We quantified the ability of GBM cells to navigate and squeeze through confined microenvironments that mimic tight perivascular conduits and white matter tracts in the brain parenchyma in vivo, as well as the proliferative capacity of highly motile subpopulations. By combining migratory- and proliferative-based indices, MAqCI correctly categorized patients into short- or long-term survival groups with high sensitivity (84%), specificity (89%), and accuracy (86%), and predicted time to recurrence. In a pilot prospective study, MAqCI classified all 5 patients accurately based on their survival outcomes. Overall, our study suggests that invasive growth is intimately linked with GBM progression and patient outcomes, and reveals the translational potential of MAqCI for personalized GBM care.
2020-09-28 | GSE144610 | GEO
Project description:Introduction: Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. Here, we sought to characterize longitudinal tumor immune microenvironment (iTME) changes in order to find potential actionable targets to prevent GBM-induced immune evasion mechanisms. This study included 15 patient-matched treatment-naïve (primary, pGBM, WHO grade 4) and recurrent (rGBM) IDH1 wild type tumors. Methods:Extracted RNA and proteins from fresh frozen tumor samples from matched pGBM and rGBM were profiled via transcriptomics and proteomics, respectively. Paired formalin-fixed paraffin-embedded tumor samples were processed for spatial transcriptomics analysis.Results: Differentially expressed genes and proteins between pGBM and rGBM were involved in pathways responsible for synapse development and myelination which have been shown to play a role in GBM recurrence. By categorizing patients into short and long time-to-relapse (STTR vs LTTR), and by correlating TTR with gene expression, we detected genes positively or negatively associated with tumor relapse. Expression of FCG receptor and complement system genes such as FCGR1A (CD64), FCGR3A (CD16a) and the complement C3 were negatively correlated with STTR, whereas high expression of DNMT1/3A, and SMARCA4, involved in DNA methylation, were positively correlated with LTTR. Spatial transcriptomic analysis of the tumor cells compartment defined by GFAP expression showed enrichment in the proportion of oligodendrocytes in recurrent tumors in rGBM, whereas CD64-positive myeloid cell compartment showed a switch of quiescent to activated microglia, appearance of B cells and a reduction in macrophage proportion in recurrent tumors with STTR. Conclusion: Our results uncover a role of CD64-expressing myeloid cells, mostly activated microglia, in GBM recurrence and suggest that interfering with these cells may represent a new therapeutic option for preventing GBM relapse.
2024-11-18 | GSE254145 | GEO
Project description:Introduction: Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. Here, we sought to characterize longitudinal tumor immune microenvironment (iTME) changes in order to find potential actionable targets to prevent GBM-induced immune evasion mechanisms. This study included 15 patient-matched treatment-naïve (primary, pGBM, WHO grade 4) and recurrent (rGBM) IDH1 wild type tumors. Methods: Extracted RNA and proteins from fresh frozen tumor samples from matched pGBM and rGBM were profiled via transcriptomics and proteomics, respectively. Paired formalin-fixed paraffin-embedded tumor samples were processed for spatial transcriptomics analysis. Results: Differentially expressed genes and proteins between pGBM and rGBM were involved in pathways responsible for synapse development and myelination which have been shown to play a role in GBM recurrence. By categorizing patients into short and long time-to-relapse (STTR vs LTTR), and by correlating TTR with gene expression, we detected genes positively or negatively associated with tumor relapse. Expression of FCG receptor and complement system genes such as FCGR1A (CD64), FCGR3A (CD16a) and the complement C3 were negatively correlated with STTR, whereas high expression of DNMT1/3A, and SMARCA4, involved in DNA methylation, were positively correlated with LTTR. Spatial transcriptomic analysis of the tumor cells compartment defined by GFAP expression showed enrichment in the proportion of oligodendrocytes in recurrent tumors in rGBM, whereas CD64-positive myeloid cell compartment showed a switch of quiescent to activated microglia, appearance of B cells and a reduction in macrophage proportion in recurrent tumors with STTR. Conclusion: Our results uncover a role of CD64-expressing myeloid cells, mostly activated microglia, in GBM recurrence and suggest that interfering with these cells may represent a new therapeutic option for preventing GBM relapse.
2024-11-18 | GSE254874 | GEO
Project description:Introduction: Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. Here, we sought to characterize longitudinal tumor immune microenvironment (iTME) changes in order to find potential actionable targets to prevent GBM-induced immune evasion mechanisms. This study included 15 patient-matched treatment-naïve (primary, pGBM, WHO grade 4) and recurrent (rGBM) IDH1 wild type tumors. Methods: Extracted RNA and proteins from fresh frozen tumor samples from matched pGBM and rGBM were profiled via transcriptomics and proteomics, respectively. Paired formalin-fixed paraffin-embedded tumor samples were processed for spatial transcriptomics analysis. Results: Differentially expressed genes and proteins between pGBM and rGBM were involved in pathways responsible for synapse development and myelination which have been shown to play a role in GBM recurrence. By categorizing patients into short and long time-to-relapse (STTR vs LTTR), and by correlating TTR with gene expression, we detected genes positively or negatively associated with tumor relapse. Expression of FCG receptor and complement system genes such as FCGR1A (CD64), FCGR3A (CD16a) and the complement C3 were negatively correlated with STTR, whereas high expression of DNMT1/3A, and SMARCA4, involved in DNA methylation, were positively correlated with LTTR. Spatial transcriptomic analysis of the tumor cells compartment defined by GFAP expression showed enrichment in the proportion of oligodendrocytes in recurrent tumors in rGBM, whereas CD64-positive myeloid cell compartment showed a switch of quiescent to activated microglia, appearance of B cells and a reduction in macrophage proportion in recurrent tumors with STTR. Conclusion: Our results uncover a role of CD64-expressing myeloid cells, mostly activated microglia, in GBM recurrence and suggest that interfering with these cells may represent a new therapeutic option for preventing GBM relapse.
2024-11-18 | GSE254873 | GEO
Project description:The purpose of this study is to determine whether the combination of two agents, INC280 and bevacizumab, is safe and effective when administered to patients with Glioblastoma Multiforme (GBM) who have progressed after receiving prior therapy or who have unresectable GBM.
| 2185625 | ecrin-mdr-crc
Project description:Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma
| PRJNA764727 | ENA
Project description:GBM samples (FFPE tissue) obtained from patients treated in clinical trials according to pre-specified clinical criteria (EORTC 26981/NCIC CE.3 pooled with the Lausanne Pilot trial, n=156).
2022-03-31 | GSE195640 | GEO
Project description:We compared whole genome expression profiles of GSCs with normal human cortex, human neural stem cells (hNSC) from fetal cortex, glioblastoma (GBM) primary, and recurrent tumors to find GSC-specific plasma membrane transcripts. All of the expression profiles were batch normalized by a robust multichip average (RMA) algorithm using Geospiza GeneSifter (PerkinElmer) online microarray database and analysis software. The data was then exported into Microsoft Office Excel 2010 and organized for GSC transcripts with raw intensity values 10 fold or higher over normal brain, hNSCs, GBM primary and recurrent tumor samples. The reverse sorting algorithm was done to obtain downregulated GSC trascripts.
2013-11-14 | E-GEOD-51822 | biostudies-arrayexpress
Project description:Patients diagnosed with glioblastomas continue to have a dismal prognosis, highlighting the need for a better characterization of these tumors in order to identify more efficient therapies. In this study, we generated genome-wide expression data from normal brain and glioma samples, representing major glioma subtypes, using exon-level microarrays (n=70). A multi-component approach was used to characterize molecular pathways and tumor infiltrate, with particular focus on the poor prognosis primary glioblastomas (pGBM). Two independent, publically available datasets were used for validation of survival data. Grade II glioma and secondary GBM were enriched in cytotoxic lymphocytes, while pGBM exhibited a heterogeneous cell-related immune infiltrate with high infiltration of monocytic cells. Infiltration by cells of monocytic origin predicted poorer prognosis, regardless of the tumor subtype. High TSPYL2 expression was found to be associated with a poor prognosis in pGBM and to correlate with genes involved in tumor invasion. The multi-component transcriptome phenotypes of pGBM introduced in this study add insights into the main pathways associated with aggressiveness, and identified infiltration by cells of monocytic origin as a universal prognostic marker for all glioma subtypes.
2018-03-01 | GSE111260 | GEO
Project description:Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples and the membranal HLA of GBM tumors of 10 tumor samples of the same patients. Tumor samples were fresh-frozen immediately after surgery and plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the same patients; yet, low correlations were observed between these HLA peptidomes and the tumors’ proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.
2019-06-11 | PXD008127 | Pride