Wang Ling, He Xiaoqin, Shen Yang, Chen Jiayu, Chen Yukai, Zhou Zhuolin, Xu Ximing
Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Curr Issues Mol Biol. 2025 Mar 18;47(3):201. doi: 10.3390/cimb47030201.
Among the most common malignant tumors, hepatocellular carcinoma (HCC) is a primary liver cancer type that has a high mortality rate. HCC often presents insidiously, is prone to recurrence, and has limited treatment efficacy. Ferroptosis regulates tumorigenesis, progression, and metastasis, which is a novel form of iron-dependent cell death. Numerous studies suggest that HCC is sensitive to ferroptosis, indicating that targeted therapies aimed at inducing ferroptosis may represent a promising new approach to cancer treatment. This study aims to find genes associated with HCC and ferroptosis, as well as to screen for potential agents that may cause ferroptosis in HCC. Transcriptome and clinical sample data were obtained from the TCGA database to identify differentially expressed genes related to ferroptosis. Using various regression and survival analysis techniques, we developed a prognostic model based on four core genes and evaluated its predictive potential. Subsequently, we screened for potential therapeutic agents in the Connective Map (CMap) database, designated as compound Atorvastatin, based on differential genes from two risk groups and related to ferroptosis. Through experiments conducted in vivo and in vitro, we demonstrated that Atorvastatin can induce ferroptosis in HCC cells while inhibiting their growth and migration. In conclusion, this research targets ferroptosis therapy and provides new insights for improving the prediction and prevention of HCC.
在最常见的恶性肿瘤中，肝细胞癌（HCC）是一种死亡率很高的原发性肝癌类型。HCC通常隐匿出现，易于复发，且治疗效果有限。铁死亡调节肿瘤发生、进展和转移，这是一种新的铁依赖性细胞死亡形式。大量研究表明HCC对铁死亡敏感，这表明旨在诱导铁死亡的靶向治疗可能是一种有前景的癌症治疗新方法。本研究旨在寻找与HCC和铁死亡相关的基因，并筛选可能在HCC中引发铁死亡的潜在药物。从TCGA数据库获取转录组和临床样本数据，以鉴定与铁死亡相关的差异表达基因。使用各种回归和生存分析技术，我们基于四个核心基因开发了一个预后模型，并评估了其预测潜力。随后，我们在连接图谱（CMap）数据库中基于来自两个风险组且与铁死亡相关的差异基因筛选潜在治疗药物，确定为阿托伐他汀化合物。通过体内和体外实验，我们证明阿托伐他汀可诱导HCC细胞发生铁死亡，同时抑制其生长和迁移。总之，本研究以铁死亡治疗为靶点，为改善HCC的预测和预防提供了新见解。
