Huang Shenglan, Liu Kan, Liu Queling, Tao Si, Wang Hua
Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi Province, 330006, P.R. China.
BMC Gastroenterol. 2025 May 8;25(1):349. doi: 10.1186/s12876-025-03951-7.
Gastric cancer (GC) is one of the most common malignant tumors with a poor prognosis. Ferroptosis is an distinct type of non-apoptotic cell death that is closely associated with tumor prognosis. Thus, we aimed to develop an novel prognosis risk model based on ferroptosis-related lncRNAs and excavate novel diagnostic markers. In this study, eight ferroptosis-related lncRNAs were obtained for constructing the prognosis model in GC based on TCGA database. The patients in the high-risk group had worse survival than those in the low-risk group, and the risk-grouping could be used as an independent prognostic factor for OS. Receiver operating characteristic curve analysis demonstrated this risk model was superior to traditional clinicopathological features in predicting GC prognosis. GSEA revealed that these lncRNAs were mainly involved in cell adhesion, cancer pathways, and immune function regulation. The key gene HAGLR of this risk signature was up-regulated in GC tissues and cells. Function assays showed that knockdown of HAGLR could effectively inhibit the GC cells proliferation and migration, whereas silencing HAGLR accelerated apoptosis and ferroptosis cell death process. In conclusion, we established a novel ferroptosis-related prognostic risk signature including eight lncRNAs, which may improve prognostic predictive accuracy for patients with GC.
胃癌（GC）是最常见的恶性肿瘤之一，预后较差。铁死亡是一种独特的非凋亡性细胞死亡类型，与肿瘤预后密切相关。因此，我们旨在开发一种基于铁死亡相关长链非编码RNA（lncRNA）的新型预后风险模型，并挖掘新的诊断标志物。在本研究中，基于TCGA数据库获得了8个铁死亡相关lncRNA，用于构建GC的预后模型。高风险组患者的生存率低于低风险组，且风险分组可作为总生存期（OS）的独立预后因素。受试者工作特征曲线分析表明，该风险模型在预测GC预后方面优于传统临床病理特征。基因集富集分析（GSEA）显示，这些lncRNA主要参与细胞黏附、癌症通路和免疫功能调节。该风险特征的关键基因HAGLR在GC组织和细胞中上调。功能实验表明，敲低HAGLR可有效抑制GC细胞增殖和迁移，而沉默HAGLR则加速细胞凋亡和铁死亡细胞死亡过程。总之，我们建立了一种包含8个lncRNA的新型铁死亡相关预后风险特征，这可能提高GC患者预后预测的准确性。
