许多研究表明，ferroptosis在癌细胞死亡中发挥重要的调控作用。尽管如此，ferroptosis调节剂在腺皮质癌（ACC）预后、肿瘤微环境免疫调节因子的表达以及免疫治疗疗效方面的潜在影响仍然大部分未知。我们使用公共ACC数据集来研究ferroptosis调节剂与预后和临床特征之间的关系。利用主成分分析算法建立了个体ACC的ferroptosis评分系统，进一步确定了与免疫调节和免疫治疗疗效有关的核心ferroptosis相关基因。 在ACC中，有20个ferroptosis调节剂表达差异明显，其中17个与ACC预后密切相关。基于ACSL4、FANCD2和SLC7A1 表达建立了ferroptosis评分系统，ferroptosis调节剂可作为ACC的独立预后因子。进一步研究表明， ferroptosis评分与肿瘤突变负荷（TMB）和免疫检查点基因表达相结合，可预测ACC的预后。RNA分离和逆转录-定量聚合酶链式反应（RT-qPCR）表明，在ACC和正常组织之间，ACSL4、FANCD2和SLC7A1 的表达水平有显著差异。此外，FANCD2在ACC中与免疫治疗疗效和预后有显著相关性。 我们的研究表明，ferroptosis与ACC的预后、临床特征、免疫检查点基因表达和肿瘤微环境免疫细胞浸润显著相关。本研究为进一步研究ACC中的ferroptosis调节剂提供了全面的证据，并为抗肿瘤免疫应答的表观遗传调控提供了新的见解。 版权所有 © 2022 Instituto Mexicano del Seguro Social (IMSS)，由Elsevier Inc.出版。保留所有权利。

Numerous studies have suggested that ferroptosis plays an important regulatory role in cancer cell death. Nonetheless, the potential effects of ferroptosis regulators on the prognosis, the expression of immunomodulatory factors in the tumor microenvironment and on the efficacy of immunotherapy in adrenocortical carcinoma (ACC) remain largely unknown.Public ACC datasets were used to investigate the relationship between ferroptosis regulators and prognosis and clinical features. A ferroptosis scoring system was established for individual cases of ACC using principal component analysis algorithms. Hub ferroptosis-related genes involved in immunoregulation and immunotherapy efficacy in ACC were further identified.Twenty ferroptosis regulators were differentially expressed in ACC and 17 ferroptosis regulators were closely related to prognosis in ACC. A ferroptosis scoring system was developed based on ACSL4, FANCD2, and SLC7A1 expression, and the ferroptosis regulators could serve as an independent prognostic factor for ACC. Further analyses indicated that the ferroptosis score integrated with the tumor mutation burden (TMB), and immune-checkpoint gene expression could predict prognosis in ACC. RNA isolation and reverse transcription‑quantitative polymerase chain reaction (RT-qPCR) demonstrated significant differences in the expression levels of ACSL4, FANCD2, and SLC7A1 between ACC and normal tissues. Furthermore, FANCD2 was significantly related to immunotherapy efficacy and prognosis in ACC.Our study demonstrated that ferroptosis was significantly associated with prognosis, clinical characteristics, immune-checkpoint gene expression, and tumor microenvironment immune cell infiltration in ACC. The current study provides comprehensive evidence for further research on ferroptosis regulators in ACC and provides new insight into the epigenetic regulation of the antitumor immune response.Copyright © 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.