• Shaokang Deng, Yaofeng Zheng, Yunzhao Mo, Xiangdong Xu, Yan Li, Yuxuan Zhang, Jie Liu, Jianqiu Chen, Yixin Tian, and Yiquan Ke.
• 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 1; 152: e436e448e436-e448.

BackgroundGlioblastoma (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.MethodsWe used differential and survival analysis and The Cancer Genome Atlas (TCGA) GBM RNA sequencing data. We also used systematic bioinformatic methods.ResultsUsing 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.ConclusionsThe 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.Copyright © 2021 Elsevier Inc. All rights reserved.

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