Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Hypothalamic-pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Diagnosis and Therapy Center for Glioma, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Comput Biol Med. 2022 Sep;148:105924. doi: 10.1016/j.compbiomed.2022.105924. Epub 2022 Aug 8.
Gliomas are malignant tumors in the central nervous system. Cuproptosis is a newly discovered cell death mechanism targeting lipoylated tricarboxylic acid cycle proteins. Previous studies have found that cuproptosis participates in tumor progression, but its role in gliomas is still elusive. Here, we systematically explored the bulk-tumor and single-cell transcriptome data to reveal its role in gliomas. The cuproptosis activity score (CuAS) was constructed based on cuproptosis-related genes, and machine learning techniques validated the score stability. High CuAS gliomas were more likely to have a poor prognosis and an aggressive mesenchymal (MES) subtype. Subsequently, the SCENIC algorithm predicted 20 CuAS-related transcription factors (TFs) in gliomas. Function enrichment and microenvironment analyses found that CuAS was associated with tumor immune infiltration. Accordingly, intercellular communications between neoplasm and immunity were explored by the R package "Cellchat". Five signaling pathways and 8 ligand-receptor pairs including ICAM1, ITGAX, ITGB2, ANXA1-FRR1, and the like, were identified to suggest how cuproptosis activity connected neoplastic and immune cells. Critically, 13 potential drugs targeting high CuAs gliomas were predicted according to the CTRP and PRISM databases, including oligomycin A, dihydroartemisinin, and others. Taken together, cuproptosis is involved in glioma aggressiveness, neoplasm-immune interactions, and may be used to assist in drug selection.
神经胶质瘤是中枢神经系统的恶性肿瘤。铜死亡是一种新发现的靶向脂酰化三羧酸循环蛋白的细胞死亡机制。先前的研究发现铜死亡参与了肿瘤的进展，但它在神经胶质瘤中的作用仍不清楚。在这里，我们系统地研究了肿瘤的 bulk-tumor 和单细胞转录组数据，以揭示其在神经胶质瘤中的作用。基于铜死亡相关基因构建了铜死亡活性评分（CuAS），并采用机器学习技术验证了评分的稳定性。高 CuAS 神经胶质瘤更有可能预后不良且具有侵袭性的间充质（MES）亚型。随后，SCENIC 算法预测了神经胶质瘤中 20 个与 CuAS 相关的转录因子（TF）。功能富集和微环境分析发现，CuAS 与肿瘤免疫浸润有关。相应地，通过 R 包“Cellchat”探索了肿瘤与免疫之间的细胞间通讯。发现了五个信号通路和 8 个配体-受体对，包括 ICAM1、ITGAX、ITGB2、ANXA1-FRR1 等，提示铜死亡活性如何将肿瘤细胞和免疫细胞联系起来。至关重要的是，根据 CTRP 和 PRISM 数据库预测了 13 种针对高 CuAS 神经胶质瘤的潜在药物，包括寡霉素 A、二氢青蒿素等。综上所述，铜死亡参与了神经胶质瘤的侵袭性、肿瘤-免疫相互作用，并且可能用于辅助药物选择。
