Adrenocortical carcinoma (ACC) is a rare malignant tumor with poor prognosis. Ferroptosis, a new form of cell death, differs from other forms of cell death and plays a vital role in tumor progress. Our study aimed to establish a ferroptosis-related signature with prognostic value in ACC. RNA-seq data and corresponding clinical characteristics for ACC were downloaded from TCGA and GEO databases. Genes included in ferroptosis risk signature were assessed by univariable and multivariable Cox regression analysis as well as lasso regression analysis. The prognostic value of the ferroptosis risk signature was assessed using K-M and ROC curves. Furthermore, we performed GSEA to discover the enriched gene sets in high-risk group. Additionally, TIMER website was applied to detect a possible connection between the signature and immune cells infiltration. ssGSEA was performed to evaluate scores of immune cells and immune-related pathways in two groups. A ferroptosis signature comprised of six genes (SLC7A11, TP53, HELLS, ACSL4, PCBP2, and HMGB1) was constructed to predict prognosis and reflect the immune infiltration in ACC. Patients in high-risk group were inclined to have worse prognosis. The ferroptosis model performed well in predicting prognosis and could be served as an independent indicator in ACC. GSEA revealed that gene sets correlated with biological processes including cell cycle, DNA replication, base excision repair, and P53 signaling pathway were highly enriched in high-risk group. In addition, we discovered that the expressional levels of hub genes were linked to six immune cells’ infiltration in ACC tumor. ssGSEA revealed that contents of most immune cells significantly decreased in the high-risk group. In conclusion, the novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in ACC. It also brings us new insights into the possible value of targeting ferroptosis during the therapy of ACC.

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鉴定与肾上腺皮质癌预后和免疫浸润相关的铁死亡相关特征

肾上腺皮质癌（ACC）是一种罕见的恶性肿瘤，预后较差。铁死亡是一种新的细胞死亡形式，不同于其他形式的细胞死亡，在肿瘤进展中起着至关重要的作用。我们的研究旨在建立具有 ACC 预后价值的铁死亡相关特征。从 TCGA 和 GEO 数据库下载 ACC 的 RNA-seq 数据和相应的临床特征。包括在铁死亡风险特征中的基因通过单变量和多变量 Cox 回归分析以及 lasso 回归分析进行评估。使用 KM 和 ROC 曲线评估铁死亡风险特征的预后价值。此外，我们进行了 GSEA 以发现高风险组中富集的基因集。此外，应用 TIMER 网站来检测特征与免疫细胞浸润之间可能存在的联系。进行ssGSEA以评估两组的免疫细胞评分和免疫相关通路。构建了由六个基因（SLC7A11、TP53、HELLS、ACSL4、PCBP2 和 HMGB1）组成的铁死亡特征，以预测预后并反映 ACC 的免疫浸润。高危组患者的预后更差。铁死亡模型在预测预后方面表现良好，可作为 ACC 的独立指标。GSEA显示与细胞周期、DNA复制、碱基切除修复和P53信号通路等生物学过程相关的基因集在高危人群中高度富集。此外，我们发现hub基因的表达水平与ACC肿瘤中6个免疫细胞的浸润有关。ssGSEA 显示，高危组大多数免疫细胞的含量显着降低。总之，新的铁死亡风险特征可用于预测预后和反映 ACC 的免疫浸润。它还为我们在 ACC 治疗期间靶向铁死亡的可能价值带来了新的见解。