Ferroptosis Suppressive Genes Correlate with Immunosuppression in Glioblastoma
Ferroptosis Suppressive Genes Correlate with Immunosuppression in Glioblastoma
复制标题
铁死亡抑制基因与胶质母细胞瘤的免疫抑制相关
DOI：
10.1016/j.wneu.2021.05.098
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发表时间：
2021-07-28
影响因子：
2
通讯作者：
Ke, Yiquan
中科院分区：
文献类型：
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作者：
Deng, Shaokang;Zheng, Yaofeng;Ke, Yiquan
背景：胶质母细胞瘤（GBM）是中枢神经系统最致命的原发性肿瘤。铁凋亡是一种程序性铁依赖性细胞死亡。在本研究中，我们的目的是确定预后铁中毒相关基因及其在肿瘤免疫中的作用。方法：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。- 结果：使用差异和生存分析，我们发现在TCGA GBM RNA测序数据中，铁凋亡抑制基因在铁凋亡相关基因中占主导地位。通过整合TCGA和基因表达综合GBM队列，检测到12个失调的铁凋亡抑制因子。在抑制因子中，CD 44、热休克蛋白家族B（小）成员1（HSPB 1）和溶质载体家族40成员1（SLC 40 A1）与总生存率相关。使用系统的生物信息学方法，我们观察到，铁凋亡抑制因子的表达与免疫抑制，这可能是由于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中毒诱导药物，对乙酰氨基酚，与CD 44，HSPB 1和SLC 40 A1相互作用。- 结论：铁凋亡抑制因子CD 44、HSPB 1和SLC 40 A1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淋巴细胞逃避）。对乙酰氨基酚可能通过调节CD 44、HSPB 1和SLC 40 A1诱导铁凋亡而发挥抗GBM的作用。我们的研究结果有望为GBM的免疫治疗提供新的策略。
-BACKGROUND: 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 ferroptosisrelated genes and their role in tumor immunity. -METHODS: We used differential and survival analysis and The Cancer Genome Atlas (TCGA) GBM RNA sequencing data. We also used systematic bioinformatic methods. -RESULTS: 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 ferroptosisinducing drug, acetaminophen, interacted with CD44, HSPB1, and SLC40A1. -CONCLUSIONS: 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.