Background: Glioma is a major cause of mortality among central nervous system tumors, with a generally poor prognosis. The lysyl oxidase (LOX) family, a group of copper-dependent amine oxidases, has been implicated in the progression of various cancers, but its specific role in glioma and its relationship with immune infiltration remains insufficiently explored. This study aims to investigate the LOX family’s expression, prognostic significance, and immune infiltration dynamics in glioma to identify potential therapeutic targets.Methods: A comprehensive analysis was conducted using public databases to assess gene expression, mutation frequency, and immune infiltration patterns related to the LOX family in glioma. The results were validated through survival analysis and immunohistochemistry. Functional assays, including EdU, Transwell, and flow cytometry, were used to evaluate glioma cell proliferation, migration, invasion, and apoptosis. Co-culture experiments with immune cells, ELISA, and a glioma transplantation model were employed to study the immune-modulatory effects of the LOX family. Gene and protein expression levels were further analyzed using qRT-PCR and Western blotting.Results: The LOX family was significantly upregulated in low-grade gliomas and strongly associated with poor clinical outcomes. Although mutation frequencies were low, the LOX family contributed to glioma progression through pathways involving metastasis, hypoxia response, angiogenesis, and immune cell infiltration. LOX expression correlated with increased infiltration of macrophages and eosinophils and decreased presence of Treg and CD8+ T cells. Knockdown of LOX genes impaired glioma cell functions, induced apoptosis, and altered immune cell behavior by reducing M2 macrophage polarization and enhancing CD8+ T cell activity.Conclusions: The LOX family is overexpressed in glioma and is associated with poor prognosis and altered immune infiltration patterns. These findings highlight the LOX family as a promising prognostic marker and therapeutic target, particularly for enhancing the effectiveness of immunotherapy in glioma treatment.

Objective : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs).Methods : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway.Results : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased.Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

The glioma tumor microenvironment (TME) exhibits profound heterogeneity that drives tumor progression and therapy resistance. By integrating single-cell RNA sequencing (eleven samples) and spatial transcriptomics (two samples), the cellular components of the glioma microenvironment were deconvoluted, revealing tumor-associated foam cells (TAFCs) as the most abundant and centrally connected subtype. The high expression of two prognostic candidate genes, growth differentiation factor 8 (GDF-8, also known as myostatin, MSTN) and transcription factor 12 (TCF12), in TAFCs was found to be correlated with poor overall survival. These two genes were associated with M2 macrophage infiltration, altered cholesterol homeostasis, and immunosuppressive signaling. Regulatory network and pathway analyses, based on computational motif enrichment and co-expression analysis, linked them to ribosome, Notch signaling, DNA repair, and cell-cycle pathways. Pseudotime trajectories revealed dynamic expression during differentiation. Additionally, drug sensitivity prediction analysis demonstrated that MSTN expression was significantly associated with sensitivity to paclitaxel and VE-822, while TCF12 expression showed potential associations with sensitivity to cytarabine, olaparib, Wee1 inhibitor, paclitaxel, and VE-822. Logistic regression analysis combining clinical parameters with MSTN and TCF12 expression effectively achieved risk stratification for glioma, with higher composite scores predicting worse 2- and 3-year survival outcomes. Calibration curves demonstrated high consistency between nomogram-predicted overall survival probabilities and actual observed outcomes. Immunofluorescence confirmed upregulated expression of MSTN and TCF12 in glioma tissues and their co-localization with macrophages. In conclusion, this study identified TAFCs as the central cells in the glioma microenvironment, with their signature genes MSTN and TCF12 representing candidate immunometabolic signatures associated with macrophage-mediated immunosuppression and metabolic reprogramming in glioma, suggesting their potential as biomarkers for patient stratification and as targets for immunometabolic therapies.