Liu Ying, Li Yufeng, Chen Li, Zha Weina, Zhang Jing, Wang Kun, Hao Chunhai, Gan Jianhe
Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, China.
Hebei Key Laboratory of Molecular Oncology, Tangshan People's Hospital, Tangshan, Hebei, 063001, China.
Curr Cancer Drug Targets. 2025;25(1):49-63. doi: 10.2174/0115680096284532231220061048.
Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Despite advancements in immunotherapy, the prognosis for patients with HCC continues to be poor. As oxidative stress plays a significant role in the onset and progression of various diseases, including metabolism-related HCC, comprehending its mechanism in HCC is critical for effective diagnosis and treatment.
This study utilized the TCGA dataset and a collection of oxidative stress genes to identify the expression of oxidative stress-related genes in HCC and their association with overall survival using diverse bioinformatics methods. A novel prognostic risk model was developed, and the TCGA cohort was divided into high-risk and low-risk groups based on each tumor sample's risk score. Levels of immune cell infiltration and the expression of immune checkpoint-related genes in different risk subgroups were analyzed to investigate the potential link between tumor immunity and oxidative stress-related features. The expression of model genes in actual samples was validated through immunohistochemistry, and their mRNA and protein expression levels were measured in cell cultures.
Four oxidative stress-related genes (EZH2, ANKZF1, G6PD, and HMOX1) were identified and utilized to create a predictive risk model for HCC patient overall survival, which was subsequently validated in an independent cohort. A correlation was found between the expression of these prognostic genes and the infiltration of tumor immune cells. Elevated expression of EZH2, ANKZF1, G6PD, and HMOX1 was observed in both HCC tissues and cell lines.
The combined assessment of EZH2, ANKZF1, G6PD, and HMOX1 gene expression can serve as an oxidative stress risk model for assessing HCC prognosis. Furthermore, there is a correlation between the expression of these risk model genes and tumor immunity.
肝细胞癌（HCC）仍然是全球最致命的癌症之一。尽管免疫疗法取得了进展，但HCC患者的预后仍然很差。由于氧化应激在包括代谢相关HCC在内的各种疾病的发生和发展中起重要作用，了解其在HCC中的机制对于有效诊断和治疗至关重要。
本研究利用TCGA数据集和一组氧化应激基因，通过多种生物信息学方法确定HCC中氧化应激相关基因的表达及其与总生存期的关联。开发了一种新的预后风险模型，并根据每个肿瘤样本的风险评分将TCGA队列分为高风险和低风险组。分析不同风险亚组中免疫细胞浸润水平和免疫检查点相关基因的表达，以研究肿瘤免疫与氧化应激相关特征之间的潜在联系。通过免疫组织化学验证实际样本中模型基因的表达，并在细胞培养物中测量其mRNA和蛋白质表达水平。
鉴定出四个氧化应激相关基因（EZH2、ANKZF1、G6PD和HMOX1），并用于创建HCC患者总生存期的预测风险模型，随后在独立队列中进行了验证。发现这些预后基因的表达与肿瘤免疫细胞浸润之间存在相关性。在HCC组织和细胞系中均观察到EZH2、ANKZF1、G6PD和HMOX1的表达升高。
联合评估EZH2、ANKZF1、G6PD和HMOX1基因表达可作为评估HCC预后的氧化应激风险模型。此外，这些风险模型基因的表达与肿瘤免疫之间存在相关性。
