Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma
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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.
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Project description:Clinical outcomes for patients with glioblastoma (GBM) are extremely poor due to inevitable tumor recurrence even after extensive treatments. These recurrences are thought to manifest from cells located within the tumor edge. Despite this, the precise molecular mechanism governing GBM spatial phenotypic heterogeneity (e.g. edge vs. core) and subsequent tumor recurrence remains poorly elucidated. Here, using patient-derived GBM core and edge tissues, we analyzed transcriptional and metabolic signatures in an effort to determine how GBM facilitates the edge phenotype and its associated recurrence-initiating cells (RICs). In so doing, we unexpectedly identified CD38 as an essential protein in the formation of the edge phenotype and found a CD38-driven interaction between edge GBM cells and neighboring astrocytes that communally develops a GBM edge that is unresectable by surgery and retains RICs.
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Project description:Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma
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Project description:Glioblastoma multiforme (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the immune system's potential against tumor cells. Our previous data showed a B-cell-based vaccine, BVax, can provide a promising therapeutic potential for GBM. In this study, we aim to characterize the antigenic reactivity of BVax-derived antibodies and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and human GBM patient samples.
2024-09-10 | PXD046712 | Pride
Project description:Circular RNAs are single-stranded covalently closed non-coding RNAs expressed in a variety of tissues and cells. Glioblastoma (GBM) is the most aggressive and lethal tumor in the central nervous system, characterized by high recurrence and mortality rates. Here we explore circRNA expression profiles in 26 primary and 3 recurrent GBM samples and compare them to healthy brain tissue. Additionally we compare expression of circRNA in GBM patients blood in comparison to healthy donor blood.
2024-06-29 | GSE196695 | GEO
Project description:Background: Glioblastoma multiforme (GBM) is the most aggressive and most lethal primary malignant brain tumor, correlated with survival rates of less than one year from the time of diagnosis. Current surgical procedure attempts to remove the bulk of the tumor mass, whereas GBM frequently recurs within 1-3cm from the primary tumor resection site. Molecular mechanisms involved in the recurrence of the tumor are still poorly understood. The aim of the study was to define the molecular signature of GBM surrounding white matter (WM) in order to better understand the molecular mechanisms involved with tumor relapse. Material & Methods: Human GBM tumor bulk and surrounding tissue (1-3cm from the border of the tumor) were obtained from five patients who underwent total tumour resection, while normal white matter was harvested from patients who underwent surgical procedure for nonmalignant pathologies. Samples were processed for hybridization on the Affymetrix Human U133A arrays and data were examined with the GeneSpring analysis software. Results: Gene expression analysis of the samples was done in 2 independent steps. First, molecular profiling comparison of GBM surrounding WM and normal WM resulted in 59 genes differentially expressed between both tissues. Among these, numerous genes expressed by mature neural cells were down-regulated in GBM surrounding WM, while gene products supporting invasion were overexpressed. Moreover, KLRC1, a specific natural killer receptor naturally involved in the activation of antitumoral cells was drastically repressed in GBM surrounding WM, suggesting that the antitumoral immune surveillance is compromised in this tissue. Second, we focused our study on genes specifically regulated in GBM periphery respectively to GBM core. The highest up-regulated gene in GBM surrounding tissue encodes for DTX4, a regulator of NOTCH signalling pathway described for its key role in maintaining neural progenitors in an uncommitted state. Conclusion: This study revealed unique molecular characteristics of GBM surrounding tissue, showing the dysregulation of genes involved in immune surveillance along with genes associated to stemness maintenance. All together, these data may help to understand the molecular mechanisms associated with GBM recurrence This study attempted to define the molecular characteristics of the GBM surrounding tissue. To this end, GBM tumor samples were obtained from 5 patients who underwent total tumor resection. Surrounding tumor mass tissue was retrieved in all cases from not infiltrated white matter sited at 2 cm from the macroscopic tumor border. Furthermore, control white matter biopsies were harvested from patients operated on for deep intracerebral cavernomas. Each sample was hybridized onto Affymetrix human U133 arrays. For each patient, tumor core sample and surrounding tissue were harvested and are identified with the same suffix number. In 2 cases, (patients 3 and 4), two tumor peripheral tissue samples were harvested and are identified with the same number followed by "R" (replicate).
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2020-12-10 | GSE155434 | GEO