Wei Hua, Peng Jiaxin
School of Resources and Environmental Science and Engineering, Hubei University of Science and Technology, Xianning 437100, China.
Research Center of Beidou, Industrial Development of Key Research Institute of Humanities and Social Sciences of Hubei Province, Hubei University of Science and Technology, Xianning 437100, China.
Int J Mol Sci. 2025 Mar 19;26(6):2779. doi: 10.3390/ijms26062779.
As a common malignancy, hepatocellular carcinoma (HCC) proliferation and metastasis could be promoted by ferroptosis and cuproptosis. In this study, we screened out the differentially expressed cuproptosis- and ferroptosis-related genes (CFRGs) and identified the 17 informative prognosis-associated genes. A CFRG scoring model was constructed based on the subtypes identified by consensus clustering analysis and principal component analysis (PCA). Furthermore, the immune profile, expression of immune checkpoint genes (ICGs) and drug susceptibility were also compared between the two CFRG score groups. The results showed that patients with a high CFRG score had higher survival probabilities. The correlation analysis suggested that CFRG scores were negatively correlated with activated CD4.T.cell. The expression patterns of thirty ICGs and the half-maximal inhibitory concentration (IC) values of 128 drugs displayed significant differences between the two CFRG score groups. A statistically significant difference in the efficacy of sorafenib was found between the two CFRG score groups. Moreover, based on multivariate COX regression analysis and weighted gene co-expression network analysis (WGCNA), we screened DLAT and SLC2A1 as signature genes. Molecular docking analysis revealed that DLAT and SLC2A1 had a strong binding affinity toward camptothecin, rapamycin, dactolisib, and luminespib. The correlation between the CFRG score and single-cell characteristics was further explored. The study depended on our understanding of the biological function of CFRGs in HCC and provided new insights for developing treatment strategies.
作为一种常见的恶性肿瘤，肝细胞癌（HCC）的增殖和转移可由铁死亡和铜死亡促进。在本研究中，我们筛选出差异表达的铜死亡和铁死亡相关基因（CFRGs），并鉴定出17个具有预后信息的相关基因。基于共识聚类分析和主成分分析（PCA）确定的亚型构建了CFRG评分模型。此外，还比较了两个CFRG评分组之间的免疫特征、免疫检查点基因（ICGs）表达和药物敏感性。结果显示，CFRG评分高的患者生存概率更高。相关性分析表明，CFRG评分与活化的CD4+T细胞呈负相关。两个CFRG评分组之间30个ICGs的表达模式和128种药物的半数抑制浓度（IC50）值存在显著差异。两个CFRG评分组之间索拉非尼疗效存在统计学显著差异。此外，基于多变量COX回归分析和加权基因共表达网络分析（WGCNA），我们筛选出DLAT和SLC2A1作为特征基因。分子对接分析显示，DLAT和SLC2A1对喜树碱、雷帕霉素、达可替尼和鲁米斯匹布具有很强的结合亲和力。进一步探讨了CFRG评分与单细胞特征之间的相关性。该研究依赖于我们对CFRGs在HCC中的生物学功能的理解，为制定治疗策略提供了新的见解。
