Department of Neurosurgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Neurosurgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
World Neurosurg. 2021 Aug;152:e436-e448. doi: 10.1016/j.wneu.2021.05.098. Epub 2021 May 29.
Glioblastoma (GBM) is the most lethal primary tumor in the central nervous system. Ferroptosis is a type of programmed iron-dependent cell death. In the present study, we aimed to identify prognostic ferroptosis-related genes and their role in tumor immunity.
We used differential and survival analysis and The Cancer Genome Atlas (TCGA) GBM RNA sequencing data. We also used systematic bioinformatic methods.
Using differential and survival analysis, we found that a ferroptosis suppressor was predominant within ferroptosis-related genes in TCGA GBM RNA sequencing data. By integrating TCGA and gene expression omnibus GBM cohorts, 12 dysregulated ferroptosis suppressors were detected. Among the suppressors, CD44, heat shock protein family B (small) member 1 (HSPB1), and solute carrier family 40 member 1 (SLC40A1) were relevant to overall survival. Using systematic bioinformatic methods, we observed that ferroptosis suppressor expression correlated with immunosuppression, which could be attributed to T-cell exhaustion and cytotoxic T-lymphocyte evasion. Finally, we observed that a potential ferroptosis-inducing drug, acetaminophen, interacted with CD44, HSPB1, and SLC40A1.
The ferroptosis suppressors CD44, HSPB1, and SLC40A1 were significantly associated with prognosis in GBM and correlated with immunosuppression (i.e., T-cell exhaustion and cytotoxic T-lymphocyte evasion). Acetaminophen might have an antitumor function in GBM by regulating CD44, HSPB1, and SLC40A1 to induce ferroptosis. Our results are expected to be of great significance in developing new immunotherapy strategies for GBM.
胶质母细胞瘤（GBM）是中枢神经系统中最致命的原发性肿瘤。铁死亡是一种程序性的铁依赖性细胞死亡。本研究旨在鉴定与铁死亡相关的预后基因及其在肿瘤免疫中的作用。
我们使用差异和生存分析以及癌症基因组图谱（TCGA）GBM RNA 测序数据。我们还使用了系统的生物信息学方法。
通过差异和生存分析，我们发现 TCGA GBM RNA 测序数据中，铁死亡相关基因中的铁死亡抑制剂占主导地位。通过整合 TCGA 和基因表达综合数据库 GBM 队列，检测到 12 个失调的铁死亡抑制剂。在这些抑制剂中，CD44、热休克蛋白家族 B（小）成员 1（HSPB1）和溶质载体家族 40 成员 1（SLC40A1）与总生存期相关。通过系统的生物信息学方法，我们观察到铁死亡抑制剂的表达与免疫抑制相关，这可能归因于 T 细胞耗竭和细胞毒性 T 淋巴细胞逃逸。最后，我们观察到一种潜在的铁死亡诱导药物，对乙酰氨基酚，与 CD44、HSPB1 和 SLC40A1 相互作用。
铁死亡抑制剂 CD44、HSPB1 和 SLC40A1 与 GBM 的预后显著相关，并与免疫抑制相关（即 T 细胞耗竭和细胞毒性 T 淋巴细胞逃逸）。对乙酰氨基酚可能通过调节 CD44、HSPB1 和 SLC40A1 诱导铁死亡从而在 GBM 中发挥抗肿瘤作用。我们的研究结果有望在为 GBM 开发新的免疫治疗策略方面具有重要意义。
