Ma Yue, Noh Che Ismail Che, Pare Rahmawati
Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Beihua University, Jilin, China.
Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Malaysia Sabah, Kota Kinabalu, Malaysia.
Transl Cancer Res. 2025 Feb 28;14(2):1157-1170. doi: 10.21037/tcr-24-1315. Epub 2025 Feb 26.
The cell death pathway, including apoptosis, autophagy, and necroptosis, plays an essential role in hepatocellular carcinoma (HCC) progression and outcome. However, the integration of the three cell death pathways into a prognostic signature has not yet been reported in HCC. This study aimed to investigate the association among cell death-related genes (CDRGs), prognosis, immune microenvironment, and immune checkpoint.
The RNA expression profiles and corresponding clinical data of HCC were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC). Univariate Cox regression analysis was performed to identify the relevant prognostic genes, and Lasso Cox regression analysis was employed to calculate the risk score. The relationship between the risk score and clinicopathological characteristics, immune cell infiltration, and immune checkpoint expression was analyzed.
A prognostic risk model for HCC was constructed from the identified CDRGs and patients were subgrouped based on risk score. High-risk patients for HCC exhibited a significantly lower overall survival (OS) rate than the low-risk patients. In addition, the receiver operating characteristic (ROC) curve demonstrated the predictive ability of the risk score. Patients in the high-risk group exhibited lower immune cell infiltration and higher expression levels of immune checkpoint molecules.
The cell death-related signature established herein provides a valuable predictive tool for survival and holds promise as a potential therapeutic biomarker for HCC.
细胞死亡途径，包括细胞凋亡、自噬和坏死性凋亡，在肝细胞癌（HCC）的进展和预后中起着至关重要的作用。然而，尚未有研究报道将这三种细胞死亡途径整合到HCC的预后特征中。本研究旨在探讨细胞死亡相关基因（CDRGs）、预后、免疫微环境和免疫检查点之间的关联。
从癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和国际癌症基因组联盟（ICGC）中检索HCC的RNA表达谱和相应的临床数据。进行单因素Cox回归分析以确定相关的预后基因，并采用Lasso Cox回归分析计算风险评分。分析风险评分与临床病理特征、免疫细胞浸润和免疫检查点表达之间的关系。
根据鉴定出的CDRGs构建了HCC的预后风险模型，并根据风险评分对患者进行亚组划分。HCC高危患者的总生存率（OS）显著低于低危患者。此外，受试者工作特征（ROC）曲线显示了风险评分的预测能力。高危组患者的免疫细胞浸润较低，免疫检查点分子的表达水平较高。
本文建立的细胞死亡相关特征为生存提供了有价值的预测工具，并有望成为HCC潜在的治疗生物标志物。
