Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184472 | GEO | 2023/05/26
REPOSITORIES: GEO
Similar Datasets
Project description:Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma
| PRJNA764727 | ENA
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: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 (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:Cell-free DNA (cfDNA) is released into the circulation from dead and dying cells, and is elevated in critical illness syndromes including sepsis and acute respiratory distress syndrome (ARDS). Plasma cfDNA has been implicated as a damage-associated molecular pattern (DAMP) that propagates ongoing inflammation. However, the tissue source of circulating cfDNA from different pathological processes has not been fully elucidated, and identification of the cellular origin of cfDNA may provide insight into the mechanisms underlying the early inflammatory response. As cfDNA retains the unique methylation pattern of its tissue of origin, we can leverage cfDNA methylome to map the presumed tissue of origin of these DAMPs. We conducted a pilot study to assess the cfDNA methylation pattern in pediatric ARDS.
2025-08-15 | GSE287137 | GEO
Project description:Aberrant hypermethylation of CpG dinucleotides located in CpG islands within the promoters of key cancer genes is an epigenetic abnormality associated with heritable transcriptional gene silencing and inactivation in cancer. The genes involved include important tumor suppressors affecting key pathways for tumor initiation and progression. These methylated sequences can serve as potentially valuable markers for cancer risk assessment, diagnosis, prognosis, and prediction of therapeutic responses. In addition, many key cancer genes may be targeted by both epigenetic and genetic alterations and, thus epigenetic analysis can help focus the search for mutations, and vice versa. Studies of major cancer types suggest that any individual patient’s tumor may harbor at least 300 or more DNA hypermethylated genes. In TCGA, a pilot project is underway to begin defining these genes for GBM via genomic approaches. The approach in the epigenetic pilot is a two-tiered one which, first, involves pharmacological treatment of both well established human GBM cell lines, and a cell line grown as a neurosphere to enrich for tumor propagating cells, with a DNA methylation inhibitor (5-aza-2’-deoxycytidine, DAC) or a histone deacetylation inhibitor (trichostatin A) followed by an expression transcriptome analysis as previously described (Schuebel et. al.). This has resulted in identification of more than 3,700 total candidate genes. In the second tier, the top candidates are then analyzed on a custom Illumina GoldenGate array with the capacity to monitor methylation at a single CpG dinucleotide in the CpG islands of 1,498 gene promoters for the high throughput analysis of TCGA GBM samples. Keywords: Microarray, Hypermethylome, DNA-hypermethylation, DAC, TSA, Epigenetic, TCGA, The Cancer Genome Atlas, GBM, Glioblastoma, Glioblastoma multiforme, Brain
2009-01-01 | GSE11233 | GEO
Project description:Translocation renal cell carcinoma (tRCC) is an aggressive fusion-driven subtype of kidney cancer that is frequently misdiagnosed due to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays targeting DNA alterations are suboptimal for use in tRCC due to its paucity of genomic changes. We demonstrate the utility of cell-free chromatin profiling to noninvasively detect and monitor tRCC with high accuracy, a method that could have applicability to other genomically quiet cancers.
2025-10-31 | GSE280708 | GEO
Project description: Not available
| S-EPMC6300090 | biostudies-literature