Assessing the Value of Disulfide Death-Associated Genes in the Prognosis and Treatment of Glioma

Abstract

Abstract Background "Disulfide death," a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes and to provide new solutions in choosing the effective treatment of glioma. Methods The combined analysis utilizes data from the Atlas of Cancer Genome (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Genotype-Tissue Expression (GTEx) databases to screen disulfide death-related genes. Then, TCGA and CGGA serve to construct and verify prognostic signature. In addition, the immunological characteristics of the model and the potential predictive value of immune and chemotherapeutic responses were further explored. Finally, the effect of Importin-4(IPO4) on gliomas has been further confirmed through functional experiments. Results 7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an independent predictor. The high-risk group exhibited immunosuppressive microenvironment, and was characterized by high concentration of M2 macrophages and regulatory T cells (Tregs). Patients in high-risk group may benefit more from immunotherapy and chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells. Conclusion This study constructed the first prognostic disulfide death-related gene signature in glioma with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.