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

串扰 胶质瘤 替莫唑胺 药品 肿瘤微环境 免疫系统 长春新碱 医学 肿瘤科 癌症研究 生物 内科学 免疫学 化疗 药理学 环磷酰胺 物理 光学
作者
Meini Yu,Diwei Huo,Kexin Yu,Kun Zhou,Fei Xu,Qingkang Meng,Yiyang Cai,Xiujie Chen
出处
期刊:Computers in Biology and Medicine [Elsevier BV]
卷期号:175: 108532-108532 被引量:4
标识
DOI:10.1016/j.compbiomed.2024.108532
摘要

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. 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. 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. 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.
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