GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses

Abstract

IntroductionGliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.MethodsThe prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. ResultsExperimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. ConclusionsThe incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.

Hypoxia‐related THBD+ macrophages as a prognostic factor in glioma: Construction of a powerful risk model

“…CHI3L1 is released into the TME, interacts with CD44 expressed on tumour‐associated macrophages, and activates the AKT pathway, thus promoting polarization of M2 macrophages. Genes like TMEM140 and GPX8 also play regulatory roles in gliomas 59,60 . These results underscore the model's pivotal predictive role in the onset and progression of gliomas.…”

“…Genes like TMEM140 and GPX8 also play regulatory roles in gliomas. 59 , 60 These results underscore the model's pivotal predictive role in the onset and progression of gliomas.…”