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Background : GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal mature astrocytes. We hypothesized that ETV6 played a role in GBM tumor progression. Methods : Expression of ETV6 was first examined in two American and three Chinese tissue microarrays. The correlation between ETV6 staining intensity and patient survival was calculated, followed by validation using public databases-TCGA and REMBRANDT. The effect of ETV6 knockdown on glioma cell proliferation (EdU), viability (AnnexinV labeling), clonogenic growth (colony formation), and migration/invasion (transwell assays) in GBM cells was tested. RNA sequencing and Western blot were performed to elucidate the underlying molecular mechanisms. Results : ETV6 was highly expressed in GBM and associated with an unfavorable prognosis. ETV6 silencing in glioma cells led to increased apoptosis or decreased proliferation, clonogenicity, migration, and invasion. RNA-Seq-based gene expression and pathway analyses revealed that ETV6 knockdown in U251 cells led to the upregulation of genes involved in extracellular matrix organization, NF-κB signaling, TNF-mediated signaling, and the downregulation of genes in the regulation of cell motility, cell proliferation, PI3K-AKT signaling, and the Ras pathway. The downregulation of the PI3K-AKT and Ras-MAPK pathways were further validated by immunoblotting. Conclusion : Our findings suggested that ETV6 was highly expressed in GBM and its high expression correlated with poor survival. ETV6 silencing decreased an aggressive in vitro phenotype probably via the PI3K-AKT and Ras-MAPK pathways. The study encourages further investigation of ETV6 as a potential therapeutic target of GBM.

High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the extent of resection has been associated with improving progression-free survival and overall survival by several months. The introduction of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery has allowed surgeons to better differentiate between neoplastic tissue and normal tissue, thus achieving greater extent of resection. The development of new intraoperative imaging modalities in combination with 5-ALA may provide additional benefits for glioma patients., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rationale : First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods : Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo , to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results : No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions : Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose of Review: In this review, we seek to summarize the literature concerning the use of single-cell RNA-sequencing for CNS gliomas., Recent Findings: Single-cell analysis has revealed complex tumor heterogeneity, subpopulations of proliferating stem-like cells and expanded our view of tumor microenvironment influence in the disease process. Although bulk RNA-sequencing has guided our initial understanding of glioma genetics, this method does not accurately define the heterogeneous subpopulations found within these tumors. Single-cell techniques have appealing applications in cancer research, as diverse cell types and the tumor microenvironment have important implications in therapy. High cost and difficult protocols prevent widespread use of single-cell RNA-sequencing; however, continued innovation will improve accessibility and expand our of knowledge gliomas.