Ma Jian-Ying, Wei Wei, Wang Yi-Xian, Zhao Zhen-Yu, Xiong Zhen-Yu, Mei Jie, Wu Wen-Ze, Guo Jia-Wei
Department of Interventional, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434020, China.
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, China.
J Cancer. 2025 Jan 1;16(2):629-647. doi: 10.7150/jca.103946. eCollection 2025.
Given the crucial role of mitochondria in the prognosis and treatment of hepatocellular carcinoma (HCC), we aim to develop two independent mitochondrial scoring systems to separately predict patient prognosis and the likelihood of transarterial chemoembolization non-response (TACE NR). Mitochondria-related candidate genes were selected and analyzed using univariate Cox and LASSO Cox regression analyses to create a risk prognosis score (RPS). Univariate and LASSO logistic regression analyses were used to establish the risk diagnosis score (RDS). Alternative therapies for patients with TACE NR were explored using TIDE and oncoPredict algorithms. The Seurat package was used to study the involvement of the RDS genes in HCC differentiation. The RPS accurately predicts the 1-5 year survival rates of patients with HCC, where higher RPS values were associated with poorer survival outcomes. The RDS model demonstrated a commendable performance in diagnosing TACE NR, as patients with a higher RDS exhibited a greater likelihood of TACE NR. RDS was associated with the infiltration of various immune cells, and patients with lower RDS tended to have higher response rates to immunotherapy and increased sensitivity to JAK1, rapamycin, and AZD2014. By contrast, patients with higher RDS values and a higher probability of TACE NR had more responsive to paclitaxel, dasatinib, and vincristine, suggesting that these drugs are potential alternative therapies. Single-cell sequencing studies have identified ACSM2A as a key player in HCC differentiation and a potential target for therapeutic intervention. The RPS and RDS are important reference points for predicting outcomes and guiding treatment decisions in patients with HCC. Additionally, ACSM2A shows promise as a potential therapeutic target for HCC.
鉴于线粒体在肝细胞癌（HCC）的预后和治疗中起着关键作用，我们旨在开发两个独立的线粒体评分系统，分别预测患者的预后以及经动脉化疗栓塞无反应（TACE NR）的可能性。选择与线粒体相关的候选基因，并使用单变量Cox和LASSO Cox回归分析进行分析，以创建风险预后评分（RPS）。使用单变量和LASSO逻辑回归分析来建立风险诊断评分（RDS）。使用TIDE和oncoPredict算法探索TACE NR患者的替代疗法。使用Seurat软件包研究RDS基因在HCC分化中的作用。RPS准确预测了HCC患者的1至5年生存率，其中较高的RPS值与较差的生存结果相关。RDS模型在诊断TACE NR方面表现出良好的性能，因为RDS较高的患者表现出更高的TACE NR可能性。RDS与各种免疫细胞的浸润有关，RDS较低的患者对免疫疗法的反应率往往较高，对JAK1、雷帕霉素和AZD2014的敏感性增加。相比之下，RDS值较高且TACE NR可能性较高的患者对紫杉醇、达沙替尼和长春新碱的反应更强，这表明这些药物是潜在的替代疗法。单细胞测序研究已确定ACSM2A是HCC分化的关键因素和治疗干预的潜在靶点。RPS和RDS是预测HCC患者预后和指导治疗决策的重要参考点。此外，ACSM2A有望成为HCC的潜在治疗靶点。
