A cell death program–based tumor signature stratifies prognosis, immune landscape, and therapeutic response in glioma

To develop a prognostic cell death–associated signature and elucidate its biological and clinical relevance in glioma.

PA.Sig stratified patients into high-and low-risk groups with significantly different overall survival.
High-risk tumors exhibited increased somatic mutation burden and enrichment of cell cycle and inflammatory pathways.
Single-cell analyses revealed MES-like and AC/MES-like states in high-risk tumors with intensified ligand–receptor interactions.
High-risk tumors showed immune dysfunction and exhaustion despite increased immune infiltration.
Chemotherapy induced both apoptotic and pyroptotic morphologies in glioma cells.

PA.Sig captures a coordinated inflammatory cell death landscape associated with aggressive cellular states and immune remodeling in glioma.

The study relies on existing transcriptomic and clinical data, which may have inherent biases.
Further validation in larger, independent cohorts is necessary to confirm findings.

PA.Sig may serve as a prognostic biomarker and provide a rationale for combinatorial strategies targeting cell death pathways and immune modulation.