Exploring the role of Disulfidptosis in glioma progression: insights into tumor heterogeneity and therapeutic potential through single-cell RNA sequencing.

BACKGROUND

Gliomas, particularly glioblastoma (GBM), are the most common and aggressive primary brain tumors in adults, characterized by high malignancy and frequent recurrence. Despite standard treatments, including surgery, radiotherapy, and chemotherapy, the prognosis for GBM remains poor, with a median survival of less than 15 months and a five-year survival rate below 10%. Tumor heterogeneity and resistance to treatment create significant challenges in controlling glioma progression. Therefore, there is an urgent need for new therapeutic targets and strategies.

OBJECTIVE

This study investigates the role of Disulfidptosis, a recently discovered form of programmed cell death, in gliomas. Unlike apoptosis and necrosis, Disulfidptosis is driven by the abnormal accumulation of intracellular disulfide bonds, leading to protein misfolding and cytoskeletal collapse, particularly in cancer cells with metabolic dysregulation. We aim to explore how glioma cells respond to Disulfidptosis and identify potential therapeutic targets by analyzing the heterogeneity of gliomas at the single-cell level using single-cell RNA sequencing (scRNA-seq).

METHODS

scRNA-seq data from glioma patients were analyzed to uncover differences in ferroptosis-related pathways, including iron metabolism and lipid peroxidation. Cellular subpopulations within gliomas were profiled to assess their sensitivity to Disulfidptosis and the underlying mechanisms. Survival analysis was conducted to evaluate the clinical relevance of Disulfidptosis-related gene expression.

RESULTS

Multiple cell subpopulations within gliomas exhibit varying sensitivities to Disulfidptosis, influenced by their metabolic properties. Dysregulated iron metabolism and antioxidant mechanisms were identified as key factors impacting Disulfidptosis sensitivity. Glioma microenvironment signaling pathways also play a role in regulating Disulfidptosis. These findings suggest that activating Disulfidptosis pathways may provide novel therapeutic strategies to overcome treatment resistance in gliomas.

CONCLUSION

This study offers new insights into the role of Disulfidptosis in glioma progression and highlights its potential as a therapeutic target. By leveraging single-cell sequencing data, the research uncovers tumor heterogeneity and identifies specific cell populations resistant to Disulfidptosis. These findings may pave the way for personalized treatment strategies to improve survival outcomes in glioma patients.