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GPX8 调控脑胶质瘤中的泛凋亡以促进小胶质细胞迁移并介导免疫治疗反应。

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

机构信息

Department of Neurosurgery, Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou, China.

Department of Radiation Oncology, The First Affiliated Hospital Zhejiang University, Hangzhou, China.

出版信息

Front Immunol. 2023 Sep 19;14:1260169. doi: 10.3389/fimmu.2023.1260169. eCollection 2023.

Abstract

INTRODUCTION

Gliomas 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.

METHODS

The 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.

RESULTS

Experimental 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.

CONCLUSIONS

The 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.

摘要

简介

近年来,神经胶质瘤已成为最主要的脑肿瘤类型,但在这方面,泛凋亡体复合物(pan-optosome complex)调控的非细胞凋亡性细胞死亡(pan-apoptosis)的探索在很大程度上仍未得到探索。本研究旨在阐明与胶质瘤患者相关的泛凋亡基因的分子特性,对其进行分类,并利用机器学习技术构建特征签名。

方法

全面研究了该签名的预后意义、突变特征、免疫特征和药物预测性能。此外,广泛研究了感兴趣的基因 GPX8,以评估其预后价值、免疫特征、药物预测性能和免疫治疗预测潜力。

结果

CCK-8、Transwell 和 EdU 等实验技术表明,GPX8 可促进神经胶质瘤中的肿瘤发生。在单细胞 RNA 测序水平上,GPX8 似乎促进了肿瘤细胞与巨噬细胞之间的细胞接触,可能增强了小胶质细胞的迁移。

结论

纳入与泛凋亡相关的特征显示出在预测肿瘤进展和推进免疫治疗策略方面具有潜在的临床应用价值。然而,需要进一步的体外和体内研究来验证与 GPX8 相关的致瘤和免疫过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d882/10545954/eb503938dd50/fimmu-14-1260169-g001.jpg

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