铁死亡是一种铁依赖性细胞死亡形式，其特征是脂质过氧化，与癌症治疗的耐药性有关，并可能导致食管鳞状细胞癌 (ESCC) 的发病机制。此外，信使 RNA (mRNA) 疫苗已成为治疗多种恶性肿瘤的一种有前景的方法。该研究的目的是调查铁死亡亚型在 ESCC 和免疫微环境中的作用，并确定可作为 mRNA 疫苗开发靶标的关键基因。对 79 名和 358 名 ESCC 患者的基因表达谱和临床数据进行了研究收集自癌症基因组图谱和基因表达综合数据库。随后，我们确定了每种铁死亡亚型的肿瘤突变负荷（TMB）、免疫微环境评分以及免疫检查点和免疫细胞功能障碍基因。此外，我们利用加权基因共表达网络分析 (WGCNA) 来描述 ESCC 的免疫景观，并确定 mRNA 疫苗开发的关键基因。我们的分析表明，MMD、MTDH 和 TRFC 是 ESCC 中过度表达的铁死亡基因。此外，ESCC被分为两种铁死亡亚型，即FS1和FS2。值得注意的是，与 FS1 相比，FS2 表现出较差的预后、较高的 TMB 和增加的免疫细胞浸润。铁死亡景观分析进一步揭示了三种不同状态的存在。 WGCNA 分析确定了不同的感兴趣模块作为独立的预后因素出现，并富含可作为 mRNA 疫苗开发目标的中心基因。铁死亡亚型与 ESCC 的预后和免疫微环境显着相关。此外，通过免疫景观分析确定的感兴趣的模块代表了一个独立的预后因素，其包含的基因组为 mRNA 疫苗的开发提供了有希望的目标。2024 转化癌症研究。版权所有。

Ferroptosis, an iron-dependent form of cell death that is characterized by lipid peroxidation, has been implicated in conferring resistance to cancer therapies and may contribute to the pathogenesis of esophageal squamous cell carcinoma (ESCC). Furthermore, messenger RNA (mRNA) vaccines have emerged as a promising modality in the treatment arsenal against diverse malignancies. The aim of the study was to investigate the role of ferroptosis subtypes in ESCC and the immune microenvironment, as well as to identify key genes that could serve as targets for mRNA vaccine development.Gene expression profiles and clinical data from 79 and 358 ESCC patients were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Subsequently, we identified tumor mutational burden (TMB), immune microenvironment scores, and immune checkpoint and immune cell dysfunction genes for each ferroptosis subtype. Furthermore, we utilized weighted gene co-expression network analysis (WGCNA) to describe the immune landscape of ESCC and identify key genes for mRNA vaccine development.Our analysis revealed that MMD, MTDH, and TRFC were overexpressed ferroptosis genes in ESCC. In addition, ESCC was categorized into two ferroptosis subtypes, namely FS1 and FS2. Notably, FS2 exhibited a poorer prognosis, higher TMB, and increased immune cell infiltration when compared to FS1. The ferroptosis landscape analysis further revealed the presence of three distinct states. WGCNA analysis identified different modules of interest emerging as an independent prognostic factor and enriched with hub genes that could serve as targets for mRNA vaccine development.The ferroptosis subtypes demonstrated significant associations with both prognosis and the immune microenvironment in ESCC. Additionally, the module of interest identified through immune landscape analysis represented an independent prognostic factor, with its contained genome offering promising targets for mRNA vaccine development.2024 Translational Cancer Research. All rights reserved.