铁死亡是一种铁依赖性程序性细胞死亡，可抑制肿瘤生长，特别是在传统的难治性肿瘤中。缺乏由铁死亡相关基因构建的预后模型；预后生物标志物仍然不足。我们从公共数据库获取了膀胱癌（BC）样本的基因表达数据和相应的临床信息。从铁死亡数据库中筛选铁死亡相关基因的临床预测价值。我们通过聚合酶链反应和蛋白质印迹验证了肿瘤和正常组织之间的基因表达差异。进行基因本体论和京都基因百科全书和基因组富集分析，以探索影响 BC 患者总体生存的信号通路。 CIBERSORT 用于量化 22 种免疫细胞类型的浸润。我们确定了 6 个基因（EGFR、FADS1、ISCU、PGRMC1、PTPN6 和 TRIM26）来构建预后风险模型。高风险组的总体生存率低于低风险组。受试者工作特征曲线显示出出色的预测准确性。验证队列和 3 个独立数据集证实了模型的普遍适用性和稳定性。 BC 组织中 FADS1、PTPN6 和 TRIM26 mRNA 和蛋白水平升高，ISCU 水平降低。富集分析表明神经分泌活性可能是影响总体生存的主要途径。高风险组和低风险组的免疫细胞浸润存在显着差异。特定的铁死亡相关基因表达与免疫细胞浸润水平相关。风险评分与患者的临床特征显着相关。建立了一种新颖的、广泛适用的、对BC患者预后具有独立预测价值的风险模型；确定了未来 BC 研究的候选分子。作者版权所有 © 2024。由 Wolters Kluwer Health, Inc. 出版

Ferroptosis is iron-dependent programmed cell death that inhibits tumor growth, particularly in traditional treatment-resistant tumors. Prognostic models constructed from ferroptosis-related genes are lacking; prognostic biomarkers remain insufficient. We acquired gene expression data and corresponding clinical information for bladder cancer (BC) samples from public databases. Ferroptosis-related genes from the ferroptosis database were screened for clinical predictive value. We validated gene expression differences between tumors and normal tissues through polymerase chain reaction and western blotting. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were conducted to explore signaling pathways affecting the overall survival of patients with BC. CIBERSORT was used to quantify the infiltration of 22 immune cell types. We identified 6 genes (EGFR, FADS1, ISCU, PGRMC1, PTPN6, and TRIM26) to construct the prognostic risk model. The high-risk group had a poorer overall survival than the low-risk group. Receiver operating characteristic curves demonstrated excellent predictive accuracy. The validation cohort and 3 independent datasets confirmed the models' general applicability and stability. BC tissues had elevated FADS1, PTPN6, and TRIM26 mRNA and protein levels and decreased ISCU levels. Enrichment analysis indicated that neurosecretory activity might be the main pathway affecting the overall survival. High- and low-risk groups had significantly different immune cell infiltration. Specific ferroptosis-related gene expression was associated with immune cell infiltration levels. The risk score was significantly correlated with patients' clinical characteristics. A novel, widely applicable risk model with independent predictive value for the prognosis of patients with BC was established; candidate molecules for future BC research were identified.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.