Crosstalk of different cell-death patterns predicts prognosis and drug sensitivity in glioma.

BACKGROUND: Glioma is a malignant brain tumor originating from glial cells, and there still a challenge to accurately predict the prognosis. Programmed cell death (PCD) plays a key role in tumorigenesis and immune response. However, the crosstalk and potential role of various PCDs in prognosis and tumor microenvironment remains unknown. Therefore, we comprehensively discussed the relationship between different models of PCD and the prognosis of glioma and provided new ideas for the optimal targeted therapy of glioma.

MATERIALS AND METHODS: We compared and analyzed the role of 14 PCD patterns on the prognosis from different levels. We constructed the cell death risk score (CDRS) index and conducted a comprehensive analysis of CDRS and TME characteristics, clinical characteristics, and drug response.

RESULTS: Effects of different PCDs at the genomic, functional, and immune microenvironment levels were discussed. CDRS index containing 6 gene signatures and a nomogram were established. High CDRS is associated with a worse prognosis. Through transcriptome and single-cell data, we found that patients with high CDRS showed stronger immunosuppressive characteristics. Moreover, the high-CDRS group was resistant to the traditional glioma chemotherapy drug Vincristine, but more sensitive to the Temozolomide and the clinical experimental drug Bortezomib. In addition, we identified 19 key potential therapeutic targets during malignant differentiation of tumor cells.

CONCLUSION: Overall, we provide the first systematic description of the role of 14 PCDs in glioma. A new CDRS model was built to predict the prognosis and to provide a new idea for the targeted therapy of glioma.