According to the World Health Organization (WHO), they are categorized by the grade of malignancy (Grades 1, 2, 3 and 4), molecular markers (e.g., IDH1/2 mutations, TERT mutations, 1p/19q co-deletion) and pathological features. They have aggressive behavior with a high mortality rate (median survival about 15 months), and exhibit notable variability at the histopathological and molecular level. Gliomas are the most common primary intracranial tumor, representing up to 80% of all brain tumors 1. Furthermore, our study brings key insights into the significant effect of GPX7 in modulating both immune molecules and in immune cell infiltration in the microenvironment of gliomas, which might impact the patient outcome, opening up future opportunities to regulate the local immune response. Combining these multiple data, we provided the first evidence regarding the epigenetic-mediated regulatory mechanisms underlying GPX7 activation in gliomas. We also found that GPX7 strongly correlates with immune cell infiltration and diverse immune cell markers, suggesting its role in tumor-specific immune response and in regulating the migration of immune cell types to the tumor microenvironment. Based on the analysis of biological functions, we found that GPX7 might be involved in immune mechanisms involving both innate and adaptive immunity, type I interferon production and regulation of synaptic transmission in LGG, whereas in GBM, it is mainly related to metabolic regulation of mitochondrial dynamics. Our results consistently demonstrated that upregulation of GPX7 is tightly modulated by epigenetic processes, which also impacted the overall survival of patients with low-grade gliomas (LGG). This upregulation was significantly linked to clinicopathological and molecular features, besides being expressed in a cell cycle-dependent manner. We discovered that GPX7 was remarkably increased in glioma tissues and cell lines, and was associated with poor prognosis. We conducted an integrated bioinformatics analysis mining GPX7 DNA methylation status, transcriptional and survival data of glioma patients. In this study, we hypothesized that GPX7 methylation status could influence biological functions and local immune responses that ultimately impact prognosis in adult gliomas. However, little is known about the function of GPX7 in gliomas. Glutathione peroxidase 7 ( GPX7) is essential for regulating reactive oxygen species homeostasis under oxidative stress. Gliomas are the most commonly occurring malignant brain tumor characterized by an immunosuppressive microenvironment accompanied by profound epigenetic changes, thus influencing the prognosis.
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