铁死亡（Ferroptosis）作为一种新型诱导的细胞程序性死亡，在癌症的发病机制中起着关键作用。然而，在胃肠间质瘤（GIST）中，铁死亡的有希望的生物标志物仍待阐明。本研究分析了GIST中与铁死亡相关基因的表达情况。在64个与铁死亡相关的基因中，转铁蛋白受体（TFRC）的表达在高风险患者中通过Gene Expression Omnibus（GEO）数据集分析呈显著上调，以及其在伊马替尼治疗后的显著变化。通过Kyoto Encyclopedia of Genes and Genomes（KEGG）通路富集分析，发现与TFRC相关的基因与细胞生长通路和代谢相关通路密切相关。此外，通过免疫组化技术，高复发风险患者更有可能表现出高TFRC表达。另外，高TFRC表达表明患者复发的不良状态，可作为复发无瘤生存（RFS）的有力独立预测因子。总而言之，我们系统总结了TFRC的表达特征和临床相关性，结果显示TFRC可作为预后因素，并在GIST中被视为潜在的治疗靶点。 版权所有 © 2023 Zhuang, Li, Yang, Ma, Shen, Huang, Pan, Cui, Ni and Wang.

Ferroptosis, as a novel-induced programmed cell death, plays critical roles in the pathogenesis of cancers. However, the promising biomarkers of ferroptosis in gastrointestinal stromal tumor (GIST) remain to be elucidated. Herein, the expression of ferroptosis-related genes was analyzed in GIST. Among the 64 ferroptosis-related genes, transferrin receptor (TFRC) expression presented a remarkable upregulation in high-risk patients through Gene Expression Omnibus (GEO) dataset analysis, as well as its significant change after imatinib was treated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of TFRC-relevant genes revealed that TFRC expression was closely associated with cell growth pathways and metabolism-related pathways. Furthermore, patients at high risk of recurrence were more likely to exhibit high TFRC expression by immunohistochemistry. Additionally, high TFRC expression indicated an undesirable state of patient relapse, which could serve as a powerful significant independent predictor of recurrence-free survival (RFS). In summary, we systematically summarize the expression characteristics and clinical relevance of TFRC and show that TFRC can be used as a prognostic factor, which can be considered a potential therapeutic target in GIST.Copyright © 2023 Zhuang, Li, Yang, Ma, Shen, Huang, Pan, Cui, Ni and Wang.