In this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC. Integrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes. Four genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy. The prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients.

中文翻译：

---

铁死亡和铁代谢特征可以有力地预测肝细胞癌的临床诊断、预后和免疫微环境

在本研究中，我们全面分析了铁死亡和铁代谢相关的基因，构建了肝癌的诊断和预后模型，并探讨了其与免疫微环境的关系。对104个铁死亡和铁代谢相关基因进行整合分析、cox回归和最小绝对收缩和选择算子（LASSO）方法以及HCC相关RNA测序，以鉴定HCC相关铁死亡和铁代谢基因。确定了四个基因（ABCB6、FLVCR1、SLC48A1 和 SLC7A11）来构建预后和诊断模型。在训练队列（P < 0.001，HR = 0.27）和测试队列（P < 0.001，HR = 0.27）中，高风险组的总生存期（OS）均低于低风险组。诊断模型成功地将 HCC 与正常样本和增殖性结节样本区分开来。与低危组相比，高危组TMB较高；巨噬细胞、滤泡辅助 T 细胞、记忆 B 细胞和中性粒细胞的比例较高；并表现出较高的 CD83、B7H3、OX40 和 CD134L 表达。作为铁死亡的诱导剂，erastin可抑制HCC细胞的增殖和进展，生物信息学分析显示其影响Th17细胞分化和IL-17信号通路，表明其是癌症免疫治疗的潜在药物。基于这四种基因的预后和诊断模型显示出优越的诊断和预测性能，为HCC患者个体化治疗提供了新的可能性。