Identification of a ferroptosis-related gene signature for predicting the prognosis of cholangiocarcinoma

Cholangiocarcinoma (CCA) is a highly intractable malignancy with poor prognosis. Ferroptosis, a newly explored type of programmed cell death, plays a critical role in the initiation and progression of a tumor. Herein, we aimed to identify a ferroptosis-related risk model to evaluate the prognosis of CCA.
Differentially expressed genes (DEGs) were retrieved from three GEO cohorts. Univariate and LASSO analysis were employed to build a ferroptosis-related gene signature. Next, the predictive value was assessed in a training and a validation cohort. Metascape Online analysis, ESTIMATE and CIBERSORT algorithms, and ssGSEA were employed to perform the functional analysis between different risk groups. Finally, the expression of prognostic genes was validated with RT-qPCR.
We identified 51 differentially expressed ferroptosis genes and established the prognostic signature containing five ferroptosis-related genes. The K-M curves and the ROC curves revealed a favorable predictive efficacy of the prognostic signature. Functional enrichment analysis indicated that immune-related responses were greatly enriched between different risk groups. Five prognostic genes were also differentially expressed in CCA cell lines.
We developed a novel ferroptosis-related gene signature for CCA with high predictive accuracy. The analysis of the immune infiltration status may provide a potential therapeutic alternative to CCA.

胆管癌（Cholangiocarcinoma, CCA）是一类预后极差的难治性恶性肿瘤。铁死亡（Ferroptosis）作为一种新兴的程序性细胞死亡类型，在肿瘤的发生与进展中发挥关键作用。本研究旨在构建与铁死亡相关的风险模型，以评估CCA患者的预后情况。
研究从三个GEO数据集队列中检索得到差异表达基因（Differentially expressed genes, DEGs）。采用单变量分析与套索回归（LASSO）分析构建铁死亡相关基因特征。随后，在训练集与验证集队列中评估该特征的预测价值。借助Metascape在线分析工具、ESTIMATE算法、CIBERSORT算法以及单样本基因集富集分析（ssGSEA），对不同风险分组间的功能特征进行分析。最终，通过实时定量聚合酶链反应（RT-qPCR）验证预后相关基因的表达水平。
本研究共筛选得到51个差异表达的铁死亡相关基因，并构建包含5个铁死亡相关基因的预后特征模型。Kaplan-Meier曲线（K-M曲线）与受试者工作特征曲线（ROC曲线）结果显示，该预后特征模型具有良好的预测效能。功能富集分析表明，不同风险分组间显著富集免疫相关生物学过程。此外，5个预后相关基因在CCA细胞系中亦呈现差异表达。
本研究开发了一种新型的CCA相关铁死亡基因特征模型，具备较高的预测准确性。对免疫浸润状态的分析可为CCA的潜在治疗策略提供新思路。