Dang Miao, Wang Siyuan, Peng Fan, Zhang Runjiao, Jiao Huanmin, Zhang Huanqin, Dong Haiying, Zhang Hongxin, Xing Jinliang, Guo Xu, Liu Yang
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, China.
Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China.
Hepatol Commun. 2025 Feb 26;9(3). doi: 10.1097/HC9.0000000000000652. eCollection 2025 Mar 1.
Transarterial chemoembolization (TACE) is the primary treatment modality for advanced HCC, yet its efficacy assessment and prognosis prediction largely depend on imaging and serological markers that possess inherent limitations in terms of real-time capability, sensitivity, and specificity. Here, we explored whether multiple features of cell-free mitochondrial DNA (cf-mtDNA), including copy number, mutations, and fragmentomics, could be used to predict the response and prognosis of patients with HCC undergoing TACE treatment.
A total of 60 plasma cell-free DNA samples were collected from 30 patients with HCC before and after the first TACE treatment and then subjected to capture-based mtDNA sequencing and whole-genome sequencing.
Comprehensive analyses revealed a clear association between cf-mtDNA multiple features and tumor characteristics. Based on cf-mtDNA multiple features, we also developed HCC death and progression risk prediction models. Kaplan-Meier curve analyses revealed that the high-death risk or high-progression-risk group had significantly shorter median overall survival (OS) and progression-free survival than the low-death risk or low-progression-risk group (all p<0.05). Moreover, the change in cf-mtDNA multiple features before and after TACE treatment exhibited an exceptional ability to predict the risk of death and progression in patients with HCC (log-rank test, all p<0.01; HRs: 0.36 and 0.33, respectively). Furthermore, we observed the consistency of change between the cf-mtDNA multiple features and copy number variant burden before and after TACE treatment in 40.00% (12/30) patients with HCC.
Altogether, we developed a novel strategy based on profiling of cf-mtDNA multiple features for prognosis prediction and efficacy evaluation in patients with HCC undergoing TACE treatment.
经动脉化疗栓塞术（TACE）是晚期肝癌的主要治疗方式，但其疗效评估和预后预测很大程度上依赖于成像和血清学标志物，这些标志物在实时性、敏感性和特异性方面存在固有局限性。在此，我们探讨了游离线粒体DNA（cf-mtDNA）的多个特征，包括拷贝数、突变和片段组学，是否可用于预测接受TACE治疗的肝癌患者的反应和预后。
从30例肝癌患者首次TACE治疗前后共收集60份血浆游离DNA样本，然后进行基于捕获的mtDNA测序和全基因组测序。
综合分析揭示了cf-mtDNA多个特征与肿瘤特征之间的明确关联。基于cf-mtDNA多个特征，我们还建立了肝癌死亡和进展风险预测模型。Kaplan-Meier曲线分析显示，高死亡风险或高进展风险组的中位总生存期（OS）和无进展生存期明显短于低死亡风险或低进展风险组（所有p<0.05）。此外，TACE治疗前后cf-mtDNA多个特征的变化在预测肝癌患者死亡和进展风险方面表现出非凡的能力（对数秩检验，所有p<0.01；HR分别为0.36和0.33）。此外，我们观察到40.00%（12/30）的肝癌患者TACE治疗前后cf-mtDNA多个特征与拷贝数变异负担之间变化的一致性。
总之，我们开发了一种基于cf-mtDNA多个特征分析的新策略，用于接受TACE治疗的肝癌患者的预后预测和疗效评估。
