坏死程序化细胞死亡（necroptosis）在肝细胞癌（HCC）的发生和肿瘤进展中起着重要作用。本研究旨在研究necroptosis在HCC的发展和进展中的作用。具体而言，我们使用与necroptosis相关的基因（NAGs）构建了一个预后预测模型，用于预测患者的结果。利用来自癌症基因组图谱（TCGA）数据库的数据，我们分析了基因表达和临床数据。我们使用CIBERSORT算法确定了与NAGs相关的5个基因模型，并探索了遗传特征和免疫细胞浸润。此外，我们进行了单细胞RNA测序，以研究necroptosis在HCC中的潜在作用。我们基于NAGs构建了一个5个基因的预后模型，在训练集和验证集中均表现出优秀的预测准确性。通过多因素Cox回归分析，我们确认了模型产生的风险评分是与预后独立相关的预测因子，优于其他临床特征。高风险评分患者的预后明显较差。为了提高necroptosis评分的临床效用，我们构建了一个准确的示意图。此外，我们比较了高风险评分和低风险评分的HCC肿瘤之间的代谢途径和免疫微环境差异。我们的单细胞RNA测序分析揭示了HCC中necroptosis主要与特定亚群的巨噬细胞相关。我们的研究揭示了HCC中存在两种不同的necroptosis亚型，并开发了一个具有异常良好预测准确性的可靠预后模型。我们观察到高风险组中M0巨噬细胞浸润显著增加。我们提出，在HCC中挽救细胞色素c代谢可能是一个潜在的治疗策略。此外，在单细胞分辨率下，我们的分析确定了骨髓细胞作为主要展示坏死程序化细胞死亡的细胞类型。具体而言，表达CD5L、CETP和MARCO的巨噬细胞可能属于一种组织驻留巨噬细胞的亚群，并且对坏死程序化细胞死亡高度敏感。这些发现提示了这个特定的巨噬细胞亚群在潜在的抗肿瘤治疗中的参与。我们的研究为预测患者预后和开发个体化治疗方法提供了新的见解。© 2023. 作者，独家授权给Springer-Verlag GmbH Germany，属于Springer Nature的一部分。

Necroptosis plays an essential role in oncogenesis and tumor progression in hepatocellular carcinoma (HCC). This study aimed to investigate the role of necroptosis in the development and progression of HCC. Specifically, we constructed a prognostic prediction model using necroptosis-associated genes (NAGs) to predict patient outcomes.Using data from The Cancer Genome Atlas (TCGA) database, we analyzed gene expression and clinical data. We identified a 5-gene model associated with NAGs and explored genetic features and immune cell infiltration using the CIBERSORT algorithm. In addition, we conducted single-cell RNA sequencing to investigate the potential role of necroptosis in HCC.We constructed a 5-gene prognostic model based on NAGs that demonstrated excellent predictive accuracy in both training and validation sets. Using multifactorial cox regression analysis, we confirmed the risk score derived from the model as an independent predictor of prognosis, surpassing other clinical characteristics. Patients with high risk scores had significantly worse prognosis than those with low risk scores. To enhance the clinical utility of the necroptosis score, we constructed an accurate nomogram. Additionally, we compared metabolic pathway and immune microenvironment differences between HCC tumors with high and low risk scores. Our single-cell RNA sequencing analyses revealed that necroptosis in HCC was primarily associated with a specific subset of macrophages.Our study revealed the presence of two distinct necroptosis subtypes in HCC and developed a robust prognostic model with exceptional predictive accuracy. We observed significantly higher infiltration of M0 macrophages in the high-risk group. We propose that rescuing cytochrome c metabolism in HCC could serve as a potential therapeutic strategy. Furthermore, at a single-cell resolution, our analysis identified myeloid cells as the primary cells exhibiting necroptosis. Specifically, macrophages expressing CD5L, CETP, and MARCO, which may belong to a subset of tissue-resident macrophages, were found to be highly susceptible to necroptosis. These findings suggest the involvement of this specific macrophage subset in potential antitumor therapies. Our study provides novel insights into predicting patient prognosis and developing personalized therapeutic approaches for HCC.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.