Background: Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy. Novel therapeutic modalities like tumor electric field therapy (TEFT) have shown promise, but underlying mechanisms remain unclear. The extracellular matrix (ECM) is implicated in GBM progression, warranting investigation into TEFT‐ECM interplay.Methods: T98G cells were treated with TEFT (200 kHz, 2.2 V/m) for 72 h. Collagen type VI alpha 1 (COL6A1) was identified as hub gene via comprehensive bioinformatic analysis based on RNA sequencing (RNA‐seq) and public glioma datasets. TEFT intervention models were established using T98G and Ln229 cell lines. Pre‐TEFT and post‐TEFT GBM tissues were collected for further validation. Focal adhesion pathway activity was assessed by western blot. Functional partners of COL6A1 were identified and validated by co‐localization and survival analysis.Results: TEFT altered ECM‐related gene expression in T98G cells, including the hub gene COL6A1. COL6A1 was upregulated in GBM and associated with poor prognosis. Muti‐database GBM single‐cell analysis revealed high‐COL6A1 expression predominantly in malignant cell subpopulations. Differential expression and functional enrichment analyses suggested COL6A1 might be involved in ECM organization and focal adhesion. Western blot (WB), immunofluorescence (IF), and co‐immunoprecipitation (Co‐IP) experiments revealed that TEFT significantly inhibited expression of COL6A1, hindering its interaction with ITGA5, consequently suppressing the FAK/Paxillin/AKT pathway activity. These results suggested that TEFT might exert its antitumor effects by downregulating COL6A1 and thereby inhibiting the activity of the focal adhesion pathway.Conclusion: TEFT could remodel the ECM of GBM cells by downregulating COL6A1 expression and inhibiting focal adhesion pathway. COL6A1 could interact with ITGA5 and activate the focal adhesion pathway, suggesting that it might be a potential therapeutic target mediating the antitumor effects of TEFT.

Background: Glioblastoma multiforme (GBM) is an aggressive malignant tumor with a high mortality rate and is the most prevalent primary intracranial tumor that remains incurable. The current standard treatment, which involves surgery along with concurrent radiotherapy and chemotherapy, only yields a survival time of 14–16 months. However, the introduction of tumor electric fields therapy (TEFT) has provided a glimmer of hope for patients with newly diagnosed and recurrent GBM, as it has been shown to extend the median survival time to 20 months. The combination of TEFT and other advanced therapies is a promising trend in the field of GBM, facilitated by advancements in medical technology.Aims: In this review, we provide a concise overview of the mechanism and efficacy of TEFT. In addition, we mainly discussed the innovation of TEFT and our proposed blueprint for TEFT implementation.Conclusion: Tumor electric fields therapy is an effective and highly promising treatment modality for GBM. The full therapeutic potential of TEFT can be exploited by combined with other innovative technologies and treatments.

Background: Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno‐oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.Methods: A quantitative meta‐analysis was conducted using the random‐effects model. Several potential factors were also reviewed qualitatively.Results: A total of 39 clinical trials were included after screening 1317 papers. Patients with O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression‐free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death‐ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non‐immunotherapy.Conclusion: Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker‐driven prospective studies are warranted.

Aims: This study aimed to discover plasma‐derived exosomal tsRNAs that serve as novel diagnostic biomarkers for glioma and to investigate the mechanism by which tsRNAs regulate glioma development. Methods: Differentially expressed tsRNAs in the plasma exosomes of glioma patients were identified using small RNA array sequencing. Bioinformatics analyses were used to predict the biological function of tsRNAs. The changes in the phenotypes of glioma cells treated with a tsRNA mimic and inhibitor were detected. The diagnostic and prognostic characteristics of potential target genes and their related functions in gliomas were further analyzed. The cell and animal experiments were used to analyze the molecular mechanisms. Results: Among the 453 differentially expressed tsRNAs identified in the plasma‐derived exosomes of glioma patients using small RNA sequencing, i‐tRF‐LeuCAA was associated with the prognosis and molecular diagnostic characteristics of glioma patients and promoted the migration, invasion, and proliferation of glioma cells and inhibited their apoptosis. In addition, TPM4 is a potential target of i‐tRF‐LeuCAA and is related to epithelial–mesenchymal transition in gliomas. Conclusions: i‐tRF‐LeuCAA could be served as a non‐invasive biomarker in the diagnosis and prognosis of glioma. i‐tRF‐LeuCAA may indirectly regulate TPM4 expression and influence epithelial–mesenchymal transition, which may promote glioma progression.

Glioma is the most common tumor in the central nervous system. High-grade gliomas confer a poor prognosis, being a serious health and economic burden. Current literature suggests the important role of long noncoding RNA (lncRNA) in mammals, especially in tumorigenesis of various tumors. The functions of lncRNA POU3F3 adjacent noncoding transcript 1 (PANTR1) have been investigated in hepatocellular carcinoma but remain yet unclear in gliomas. We evaluated the role of PANTR1 in glioma cells using published data from The Cancer Genome Atlas (TCGA), then validated it by ex vivo experiments. To investigate the potential cellular mechanism of different levels of PANTR1 expression in glioma cells, we used siRNA-mediated knockdown in low-grade (grade II) cell lines and GBM (grade IV) cell lines (SW1088 and SHG44, respectively). On the molecular level, low expression of PANTR1 caused significantly reduced glioma cell viability and enhanced cell death. Moreover, we identified the importance of PANTR1 expression for cell migration in both cell lines, a critical foundation for invasiveness in recurrent gliomas. In conclusion, this study provides the first evidence that PANTR1 has a relevant role in human glioma by influencing cell viability and cell death.