Rationale: Glioblastoma (GBM), the most aggressive primary tumor of the central nervous system, remains clinically intractable because of marked molecular heterogeneity and persistent therapeutic resistance, underscoring the need for novel targeted interventions. Methods: Gene expression profiles from the TCGA and CGGA datasets were analyzed to identify prognostic transcription factors. Functional validation was performed using lentiviral-mediated knockdown and overexpression in GBM cell lines, followed by assays for proliferation, migration, invasion and apoptosis. Underlying molecular mechanisms were investigated using chromatin immunoprecipitation (ChIP), co-immunoprecipitation (co-IP), ubiquitination assays, and in vitro kinase assays. A nanocapsule-based siRNA delivery system was engineered and evaluated for its stability, cellular uptake, and blood-brain barrier penetration. Therapeutic efficacy was assessed in orthotopic GBM models using bioluminescence imaging, survival analysis, and histopathological examination. Results: This study identified FOS-like antigen 1 (FOSL1) as a key oncogenic driver that facilitates GBM progression through a positive feedback loop with inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα). Mechanistic studies revealed that FOSL1 enhances transcriptional upregulation of IKKα, while IKKα reciprocally stabilizes FOSL1 by suppressing its phosphorylation and subsequent ubiquitin-proteasomal degradation. Ubiquitination assays further identified ubiquitin C-terminal hydrolase L3 (UCHL3) as the principal de-ubiquitinase mediating FOSL1 stabilization through selective removal of K48-linked polyubiquitin chains. This FOSL1-driven positive feedback loop ultimately activated NF-κB signaling, resulting in enhanced invasion and malignancy of GBM. From a therapeutic standpoint, targeting the FOSL1/IKKα/UCHL3 feedback axis yielded significant attenuation of multiple malignant phenotypes of GBM using a novel nanoparticle-based siRNA delivery system (plofsome@siFOSL1), which effectively suppressed FOSL1 expression. Conclusions: The findings of this study establish a previously unrecognized FOSL1/IKKα/UCHL3 positive feedback loop as a central driver of GBM pathogenesis through activation of NF-κB signaling, providing a promising molecular target for future GBM therapeutic strategies.

Temozolomide (TMZ) resistance is a critical factor that affects the therapeutic efficacy in glioblastoma (GBM). Glutathione peroxidase 8 (GPX8), a ROS scavenging enzyme, is associated with poor prognosis in GBM. In this study, we comprehensively studied the role and mechanism of GPX8 in GBM resistance to TMZ. We found that GPX8 was upregulated in GBM cells, tissues, and TMZ-resistant GBM cells. In U87 TMZ-resistant cells, GPX8 knockdown significantly suppressed cell proliferation, reversed the epithelial-mesenchymal transition (EMT), and sensitized cells to TMZ. Moreover, GPX8 knockdown induced mitochondrial oxidative stress, leading to apoptosis in TMZ-resistant cells. TEA domain family member 4 (TEAD4) was upregulated in GBM cells and transactivates GPX8. GPX8 interacted with collagen triple helix repeat containing-1 (CTHRC1) and promoted its expression. Overexpression of TEAD4 or CTHRC1 reversed the suppressive effect of GPX8 knockdown on the malignant phenotypes of TMZ-resistant cells and antagonized its promotive effect on mitochondrial ROS generation and apoptosis. Furthermore, overexpression of GPX8 or CTHRC1 promoted EMT, reduced ROS levels, and lowered TMZ sensitivity in resistant cells. Crucially, the p38 MAPK/FOXO3 pathway inhibitor Ade was able to reverse these effects. GPX8 knockdown increased GBM sensitivity to TMZ, inhibited EMT, and elevated ROS levels in both xenograft models and glioma organoids. Overall, our results elucidated that TEAD4-driven GPX8 suppresses mitochondrial oxidative stress in TMZ-resistant cells through activation of the CTHRC1/p38 MAPK/FOXO3 pathway, which promotes TMZ resistance in GBM cells. These findings suggest that GPX8 may serve as a novel therapeutic target for overcoming TMZ resistance in GBM.

Platinum-based chemotherapy remains a cornerstone of glioma treatment, yet resistance driven by the Fanconi anaemia (FA) DNA repair pathway limits efficacy. Here, we identified betulinic acid (BA) as a potent inhibitor of FA pathway activation. BA pretreatment abrogated cisplatin-induced monoubiquitination of FANCI/FANCD2 and disrupted their nuclear foci formation and interactions with downstream repair proteins (ERCC1, REV1 and BRCA1), leading to persistent DNA interstrand crosslinks without affecting intrastrand lesion repair. Biochemical analyses revealed that BA selectively suppressed UBE2T expression at the transcriptional level, without altering mRNA stability or protein degradation, thereby blocking the FANCL-UBE2T-mediated ID2 monoubiquitination cascade. In vivo, BA significantly enhanced the antitumour efficacy of cisplatin in xenograft models. Mechanistically, BA inhibited MAPK/ERK signalling, and pharmacological reactivation of ERK reversed BA-induced suppression of UBE2T and tumour growth. Collectively, these findings uncover a previously unrecognised MAPK/ERK-UBE2T-FA axis in glioma and highlight BA as a potential adjuvant to overcome cisplatin resistance through transcriptional repression of UBE2T.

Background Glioblastoma (GBM) is a treatment-challenging disease with a poor prognosis and few treatment options available. Patients with GBM with BRAF gene mutations are expected to benefit from targeted therapy with BRAF inhibitors.Methods Genomic profiles, clinical and sample data, and tumor pathways were retrieved in a cohort of GBM patients with BRAF gene alterations. Statistical analysis was performed according to BRAF AMP, BRAF V600E, and BRAF non-V600E to study clinical features, survival curve analysis, tumor site, tumor signaling pathway and molecules.Results BRAF AMP and BRAF MUT include BRAF V600E and BRAF non-V600E in GBM patients account for the majority of BRAF-altered GBM. The prognosis of GBM patients with BRAF AMP is worse than that of patients with BRAF MUT, as well as BRAF V600E and BRAF non-V600E. The temporal lobe was primarily affected in GBM patients who carry BRAF gene alterations. CDKN2A DeepDel is a mutation associated with the BRAF variant GBM. In addition, BRAF AMP is often accompanied by amplified oncogenes, including MET, RHEB, and CUL1, as well as multiple types of mutations result in tumor suppressor genes in patients with BRAF non-V600E GBM including NF1 and TP53.Conclusions Different BRAF gene alterations affect the prognosis of GBM and are associated with molecular alterations in classical tumor signaling pathways, and BRAF AMP is often accompanied by amplification of MET, RHEB, and CUL1.

Glioblastoma (GBM) remains one of the most aggressive and therapy-resistant malignancies of the central nervous system, with anoikis resistance emerging as a critical facilitator of tumor invasion and therapeutic failure. In this study, we identified cathepsin Z (CTSZ) as a pivotal regulator of anoikis resistance in GBM. Clinical data revealed significant elevation of CTSZ levels in GBM tissues, with its expression strongly correlating with adverse patient outcomes. Through comprehensive functional analysis, we determined that genetic knockdown of CTSZ substantially increased anoikis sensitivity in GBM cells while simultaneously attenuating multiple oncogenic characteristics. Mechanistically, we established that CTSZ-mediated anoikis resistance enhanced multiple malignant traits of GBM by activating nuclear factor kappa B (NF-κB) signaling, as evidenced by the impaired nuclear translocation of p65 following CTSZ-knockdown. Our findings collectively position the CTSZ/NF-κB axis as a crucial determinant of GBM pathogenesis and highlight CTSZ as a potential therapeutic target for this devastating disease.

Glioblastoma (GBM) is the most fatal primary brain malignancy in adults, with a median survival of approximately 15 months. The 2021 WHO classification redefined GBM as exclusively IDH-wildtype based on its characteristic molecular and clinical features. In this study, we aimed to identify key prognostic genes in GBM, IDH-wildtype. Using univariate Cox proportional hazards regression analysis, PXN was identified as a critical upregulated gene in GBM, IDH-wildtype, significantly associated with poor prognosis. Its expression was further validated by qRT-PCR, western blotting, and immunohistochemistry. Functional assays revealed that elevated PXN enhances GBM malignancy, whereas its knockdown suppresses corresponding malignant features. Mechanistically, PXN and STAT3 form a positive feedback loop: STAT3 upregulates PXN transcription, and PXN, in turn, activates STAT3 by regulating SRC transcription. Additionally, PXN stabilizes YB-1 protein by inhibiting its ubiquitination. Further mRNA sequencing analysis demonstrated that YB-1 contributes to maintaining GBM malignancy through multiple signaling pathways. These results suggest that the STAT3-PXN positive feedback axis and the regulation of YB-1 stability by PXN may offer novel targets for GBM therapy.PXN is elevated in GBM, IDH-wildtype and associated with poor prognosis and malignant features. STAT3 directly promotes PXN transcription, and PXN reciprocally activates STAT3 by regulating SRC transcription. PXN stabilizes YB-1 protein by inhibiting its ubiquitin-mediated degradation.

As one of the most prevalent primary brain tumors, glioblastoma (GBM) is characterized by its severe malignancy and extremely poor prognosis. Recent studies have demonstrated that targeting anoikis and malignancy showed impressed efficiency for treatment in a wide range of solid tumors, however, relevant research on GBM still remains unclarified. In this study, genes related with malignancy and anoikis of GBM were identified by utilizing the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and the Molecular Signatures Database (MSigDB). Subsequently, the role of the key gene was validated via proliferation, invasion and migration experiments both in conditions with and without attachment. Moreover, RNA sequencing analysis was employed to reveal further mechanisms. Here, Type V collagen alpha 1 (COL5A1) was identified as a critical gene associated with anoikis and poor outcomes. Additionally, COL5A1 knockdown induced significant reduction in malignancy of GBM both in vitro and in vivo. Moreover, cell anoikis was remarkable enhanced by reduced expression of COL5A1 after low-attachment cell culture. Mechanically, RNA sequencing analysis revealed that the activity of the Wnt/β-catenin signaling pathway was diminished following COL5A1 knockdown, which indicated that COL5A1 reduced anoikis via regulating Wnt/β-catenin signaling pathway thus promoted malignancies of GBM cells. These findings demonstrated the novel evidence that COL5A1 serves as an essential regulatory factor influencing both anoikis and malignancy of GBM cells by regulating Wnt/β-catenin signaling pathway, indicating that COL5A1 could be a novel prognosis-related biomarker and potential therapeutic target for GBM.

Glioblastoma (GBM) exhibits profound genetic heterogeneity and poor prognosis, and a wide range of biological processes are proved to be enrolled in its tumorigenesis and progression. Necroptosis, which is identified as a regulated cell death process, has been widely confirmed to be essential in shaping malignant behaviors among multiple tumors; nevertheless, the functions of necroptosis in GBM still remain elusive. Herein, matrix metalloproteinase-14 (MMP14) was identified as a necroptosis-related hub gene in GBM by using weighted gene co-expression network analysis (WGCNA) of bulk transcriptomic data. Moreover, single-cell analysis and spatial transcriptomics mapped a cell subpopulation in which MMP14 and necroptosis are closely correlated. Additionally, MMP14 emerged as a poor prognostic marker in GBM. Functionally, knockdown of MMP14 suppressed GBM malignant behavior, including proliferation, immigration, invasion, and tumorigenesis, with an increased susceptibility to necroptosis. As an underlying mechanism, TGF-β signaling was critical for MMP14-mediated necroptosis activation, with SMAD Family Member 2 (SMAD2) directly binding to the Receptor-Interacting Protein 1 (RIP1) promoter. Altogether, MMP14 promotes a range of malignant behaviors and orchestrates a TGF-β-dependent necroptosis heterogeneity landscape in GBM; therefore, targeting MMP14-TGF-β signaling could be a novel strategy to counteract therapeutic resistance in GBM.

Epilepsy is a neurological disorder that can affect individuals of all genders and ages. Recent studies have indicated that the Mediterranean diet exerts a neuroprotective effect through its anti-inflammatory and antioxidant properties in non-Mediterranean regions. However, the association between the Mediterranean diet and epilepsy requires further elucidation. A total of 14,259 participants were enrolled in this study from the National Health and Nutrition Examination Survey (NHANES) database, spanning the period from 2013 to 2018. Weighted logistic regression analysis assessed the association between Mediterranean diet adherence and epilepsy. Random forest analysis was conducted to evaluate the relative importance of diet components. Furthermore, mediation analysis with bootstrapping was employed to explore the mediating role of epilepsy. After adjusting for all potential covariates, higher Mediterranean diet adherence was associated with a lower risk of epilepsy (OR = 0.50, 95

The mortality rates have been increasing for glioma in adolescents and young adults (AYAs, aged 15-39 years). However, current biomarkers for clinical assessment in AYAs glioma are limited, prompting the urgent need for identifying ideal prognostic signature. Extracellular matrix is involved in the development of tumors, while their prognostic significance in AYAs glioma remains unclear. By an integrated machine learning workflow and circuit training and validation procedure, we developed a machine learning-derived prognostic signature (MLDPS) based on 1,026 extracellular matrix-related genes and 3 AYAs glioma cohorts. MLDPS exhibited robust and consistent predictive performance in overall survival and could serve as an independent prognostic factor for AYAs glioma. Simultaneously, MLDPS outperformed previous 89 published prognostic signatures and traditional clinical characteristics, confirming the robust predictive capability. Besides, MLDPS had the potential to stratify prognosis in patients with other cancer types. In addition, the tumor microenvironment between high and low MLDPS groups displayed different patterns while more tumor-infiltrating immune cells were observed in high MLDPS group. Additionally, patients in low MLDPS group had significantly prolonged survival when received immunotherapy in cancers including glioblastoma, urothelial carcinoma and melanoma. Overall, our study proposes a promising signature, which can be utilized for clinicians to evaluate prognosis and might provide individualized clinical management for AYAs glioma.

BACKGROUND:Augmented reality (AR) has been widely used in neurosurgery in recent years. The combination of AR and brain surface morphology for localization has not been reported. The aim of this work was to report the outcomes of combined method for locating supratentorial lesions in neurosurgery. METHODS:After multimodal image registration, brain tissue, the lesion, and blood vessels were reconstructed using a three-dimensional Slicer. AR was conducted using a smartphone application named Persp three-dimensional to project intracranial lesions on the scalp. The incision and size of the craniotomy were designed according to the location of the lesions. After craniotomy, the lesions were precisely located using brain surface morphology. Three types of morphology were used to localize the lesions: 1) the morphology of sulci and gyri; 2) superficial cerebral veins; and 3) combination of both. Then, the lesions were resected. Postoperative magnetic resonance imaging confirmed the extent of the resection. RESULTS:Of the 34 patients included in this study, 13 (38.2%) had gliomas, 15 (44.1%) had focal cortical dysplasia, and 6 (17.6%) had cavernous hemangiomas. The first type of morphology was used in 8 (23.5%) patients, the second type in 5 (14.7%), and the third in 21 (61.8%). In all cases, the lesions were accurately located and completely removed. No complications were recorded. CONCLUSIONS:AR combined with brain surface morphology could accurately locate lesions. This combined approach is convenient to use, and helpful for planning craniotomy and removing lesions.

Objective: This study aimed to examine the association of the systemic immune-inflammation index (SII) with stroke and mortality rates using data from the National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional study was conducted using the aggregated data from 5 cycles (2009 to 2018) of NHANES. SII was the independent variable, and stroke was the dependent variable. Weighted logistic regression models were employed to analyze their relationship. The nonlinear association between SII and stroke was examined using the restricted cubic spline (RCS) method in subgroups stratified by smoking status, hypertension, and dietary inflammatory index. Weighted Kaplan-Meier curves and Cox regression analysis were used to investigate the association of SII with all-cause mortality and cardiovascular disease (CVD) mortality. Results: A total of 22,107 samples were included in this study. Weighted logistic regression analysis showed a significant correlation between SII and stroke (OR: 1.53, 95% CI: 1.22-1.92, P<0.001). The stratified analysis revealed that interactions of smoking status and hypertension with SII, respectively, had significant impacts on stroke risk. A remarkable positive link between SII and stroke risk (OR>1, P<0.05) was observed in the crude model (unadjusted for confounding factors), model I (adjusted for demographic characteristics), and model II (adjusted for all confounding factors). RCS analysis displayed a remarkable nonlinear positive correlation between SII and stroke risk only in the "now smoking" population (P-nonlinear<0.05) after adjusting for all confounding factors. In the overall sample population, Kaplan-Meier curves indicated that individuals in the highest quartile of SII had the highest risk of all-cause mortality and CVD mortality (log-rank test P<0.05). Samples with proinflammatory dietary habits had considerably higher risks of all-cause mortality and CVD mortality compared with those with anti-inflammatory dietary habits (log-rank test P<0.05). Multivariable-adjusted Cox regression models showed significantly increased all-cause mortality and CVD mortality rates in the highest quartile of SII compared with the lowest quartile. Conclusions: SII levels were considerably positively linked to stroke risk, particularly in the "now smoking" population. Moreover, elevated SII levels increased the risk of all-cause mortality and CVD mortality in the overall population. On the basis of these findings, we recommend incorporating smoking cessation measures into stroke risk reduction strategies.

OBJECTIVE:This study aimed to examine the association of the systemic immune-inflammation index (SII) with stroke and mortality rates using data from the National Health and Nutrition Examination Survey (NHANES). METHODS:A cross-sectional study was conducted using the aggregated data from 5 cycles (2009 to 2018) of NHANES. SII was the independent variable, and stroke was the dependent variable. Weighted logistic regression models were employed to analyze their relationship. The nonlinear association between SII and stroke was examined using the restricted cubic spline (RCS) method in subgroups stratified by smoking status, hypertension, and dietary inflammatory index. Weighted Kaplan-Meier curves and Cox regression analysis were used to investigate the association of SII with all-cause mortality and cardiovascular disease (CVD) mortality. RESULTS:A total of 22,107 samples were included in this study. Weighted logistic regression analysis showed a significant correlation between SII and stroke (OR: 1.53, 95% CI: 1.22-1.92, P <0.001). The stratified analysis revealed that interactions of smoking status and hypertension with SII, respectively, had significant impacts on stroke risk. A remarkable positive link between SII and stroke risk (OR>1, P <0.05) was observed in the crude model (unadjusted for confounding factors), model I (adjusted for demographic characteristics), and model II (adjusted for all confounding factors). RCS analysis displayed a remarkable nonlinear positive correlation between SII and stroke risk only in the "now smoking" population ( P -nonlinear<0.05) after adjusting for all confounding factors. In the overall sample population, Kaplan-Meier curves indicated that individuals in the highest quartile of SII had the highest risk of all-cause mortality and CVD mortality (log-rank test P <0.05). Samples with proinflammatory dietary habits had considerably higher risks of all-cause mortality and CVD mortality compared with those with anti-inflammatory dietary habits (log-rank test P <0.05). Multivariable-adjusted Cox regression models showed significantly increased all-cause mortality and CVD mortality rates in the highest quartile of SII compared with the lowest quartile. CONCLUSIONS:SII levels were considerably positively linked to stroke risk, particularly in the "now smoking" population. Moreover, elevated SII levels increased the risk of all-cause mortality and CVD mortality in the overall population. On the basis of these findings, we recommend incorporating smoking cessation measures into stroke risk reduction strategies.

- BACKGROUND: Surgery is effective in the treatment of epilepsy, particularly focal epilepsy. The aim of this work was to report the incidence and grade of severity of hemorrhagic complications after cranial epilepsy surgery, and investigate the risk factors. - METHODS: Patients who underwent epilepsy surgery via craniotomy between October 2003 and April 2019 were retrospectively analyzed. The incidence of hemorrhagic complications occurring in a 3 -month period after cranial surgery was recorded. Other outcomes included the grade of hemorrhagic severity and risk factors. - RESULTS: During the inclusion period, 2026 surgical procedures were performed. Sixty-six hemorrhagic complications were recorded. The total incidence of hemorrhagic complications after cranial epilepsy surgery was 3.3%. The most common type of hemorrhagic complications was epidural hemorrhage (57.6%), followed by intraparenchymal hemorrhage (33.3%). Forty-five patients (68.2%) had grade I complications, 4 (6.1%) grade II, 16 (24.2%) grade III, and 1 (1.5%) grade IV. The mortality due to hemorrhagic complications was 1.5% (1 of 66) and hemorrhagic mortality among all cranial surgery was 0.05% (1 of 2026). Left craniotomy induced a higher percentage of severe hemorrhage than the right (34.2% vs. 14.3%). Extratemporal lobe epilepsy induced a higher percentage of severe hemorrhage than other epilepsy type (34.2% vs. 14.3%). However, no statistically significant difference was observed between these two factors ( P [ 0.067). - CONCLUSIONS: Hemorrhagic complications were uncommon after open surgery for epilepsy. Most hemorrhagic complications were mild while the severe were rare. Patients with hemorrhagic complications had a good prognosis after effective treatment.

Intracranial aneurysms (IAs) often go undetected until rupture, leading to significant morbidity and mortality. Identifying biomarkers for early detection of IAs is crucial. The current study attempted to identify core genes linked with IAs and determine their relevance through Mendelian randomization. Limma helped identify differentially expressed genes between IAs and control superficial temporal artery samples. WGCNA was utilized to find IA-related modules and associated genes, which were further evaluated using KEGG and GO analyses to ascertain their potential roles. Five highly associated genes were screened with the CytoHubba plugin of Cytoscape software. ROC curves assessed the diagnostic efficacy of these genes. A two-sample Mendelian randomization evaluated the causal relationship between the core gene PTRPC and IAs, along with its correlation with immune infiltration. WGCNA and differential expression analysis depicted 584 related genes involved in cellular metabolism and chemokine activity. PTPRC was among the top highly associated genes identified through Cytoscape. It showed significant diagnostic value for IAs. Moreover, mendelian randomization depicted that PTPRC in CD4+ T cells is related to IA risk, with an OR of 0.63538 (95 % CI = 0.41636-0.96959, p = 0.03545). No reverse causal relationship was observed between PTPRC and IAs, with an OR of 0.99947 (95 % CI = 0.99719-1.00176, p = 0.65022). Additionally, immune cell infiltration results indicated a positive correlation between PTPRC in IAs with neutrophils and unactivated dendritic cells and a negative association with regulatory T cells (Tregs). PTPRC was identified as a core gene linked with IAs, providing evidence for IA diagnosis and studying molecular mechanisms.

Glioblastoma (GBM) is characterized by significant heterogeneity, leading to poor survival outcomes for patients, despite the implementation of comprehensive treatment strategies. The roles of cyclin A2 (CCNA2) and NIMA related kinase 2 (NEK2) have been extensively studied in numerous cancers, but their specific functions in GBM remain to be elucidated. The present study aimed to investigate the potential molecular mechanisms of CCNA2 and NEK2 in GBM. CCNA2 and NEK2 expression and prognosis in glioma were evaluated by bioinformatics methods. In addition, the distribution of CCNA2 and NEK2 expression in GBM subsets was determined using pseudo-time analysis and tricycle position of single-cell sequencing. Gene Expression Omnibus and Kyoto Encyclopedia of Genes and Genome databases were employed and enrichment analyses were conducted to investigate potential signaling pathways in GBM subsets and a nomogram was established to predict 1-, 2- and 3-year overall survival probability in GBM. CCNA2 and NEK2 expression levels were further validated by western blot analysis and immunohistochemical staining in GBM samples. High expression of CCNA2 and NEK2 in glioma indicates poor clinical outcomes. Single-cell sequencing of GBM revealed that these genes were upregulated in a subset of positive neural progenitor cells (P-NPCs), which showed significant proliferation and progression properties and may activate G2M checkpoint pathways. A comprehensive nomogram predicts 1-, 2- and 3-year overall survival probability in GBM by considering P-NPCs, age, chemotherapy and radiotherapy scores. CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle, thus indicating the potential of novel therapy directed to CCNA2 and NEK2 in GBM.

Brain-computer interface (BCI) has been widely used in the field of medical rehabilitation related to hand movement. However, the single-handed multi-class movement recognition has remained mostly unexplored. In order to improve the accuracy of hand movement classification, an algorithm using dynamical graph convolutional neural network (DGCNN) in electroencephalogram (EEG) source space (sDGCNN) was proposed in this paper. The algorithm firstly maps EEG signals to source space by spatial source localization method. Secondly, time-domain features are extracted from each brain region. Finally, the graphs with brain regions as nodes and extracted features as node values are input into DGCNN for four-classification. The signals in γ band (30−100 Hz) reached the highest accuracy of 90.16 ± 6.8

BACKGROUND:The tumor microenvironment contains chemokines that play a crucial role in various processes, such as tumorigenesis, inflammation, and therapy resistance, in different types of cancer. CXCL5 is a significant chemokine that has been shown to promote tumor proliferation, invasion, angiogenesis, and therapy resistance when overexpressed in various types of cancer. This research aims to investigate the impact of CXCL5 on the biological functions of glioblastoma (GBM).METHODS:The TCGA GBM and GEO databases were utilized to perform transcriptome microarray analysis and oncogenic signaling pathway analysis of CXCL5 in GBM. Validation of CXCL5 expression was performed using RT-qPCR and Western Blot. The impact of CXCL5 on cell proliferation, tumorigenesis, and angiogenesis in GBM was assessed through various methods, including cell proliferation assay, cloning assay, intracranial xenograft tumor models, and tube formation assay. Clinical prognosis was evaluated in 59 samples of gliomas with varying degrees of malignancy (grades 2, 3, and 4) and the TCGA GBM database, based on CXCL5 expression levels. The activities of the JAK-STAT and NF-κB signaling pathways were detected using Western Blot.RESULTS:The expression of CXCL5 was highly enriched in GBM. Moreover, the inhibition of CXCL5 showed a significant efficacy in suppressing cellular proliferation and angiogenesis, resulting in extended survival rates in xenograft mouse models in comparison to the control group. Notably, pretreatment with dapsone exhibited a reversal of the impact of CXCL5 on the formation of colonies and tubes in GBM cells. Elevated expression of CXCL5 was correlated with poor outcomes in GBM patients. Furthermore, the overexpression of CXCL5 has been associated with the activation of JAK-STAT and NF-κB signaling pathways.CONCLUSIONS:CXCL5 plays an important role in tumorigenesis and angiogenesis, indicating the potential for novel therapies targeting CXCL5 in GBM.