肝细胞癌（HCC）患者中肿瘤免疫微环境的异质性是预后不良的主要因素。最近的单细胞研究表明，中性粒细胞在HCC免疫微环境中发挥着重要作用。然而，仍然需要根据中性粒细胞的异质性对HCC患者进行分层。因此，开发一种能有效描述HCC患者中的“中性粒细胞特征”的方法对于指导临床决策至关重要。 我们使用批量测序和单细胞测序数据将两个HCC患者队列分成与中性粒细胞相关的分子亚型。此外，我们通过整合101个预测模型的机器学习分析构建了一个新的风险模型。我们比较了患者亚组之间的生物学和分子特征，以评估模型的有效性。此外，通过分子生物学实验证实了本研究中鉴定的一个重要基因。 我们将HCC患者分成了展现出预后、临床病理特征、炎症相关途径、免疫浸润水平和免疫基因表达水平等显著差异的亚型。此外，我们使用机器学习构建了一个名为“中性粒细胞衍生特征”（NDS）的风险模型，其中包含了10个关键基因。 NDS的风险评分展现了超越临床变量的准确性，并与较高度的恶性程度相关。风险评分是HCC患者总生存的独立预后因子，也展现了对HCC患者预后的预测价值。此外，我们观察到风险评分和免疫治疗和化疗药物疗效之间的关联。 我们的研究突显了中性粒细胞在HCC肿瘤微环境中的关键作用。开发的NDS是评估HCC风险和临床治疗的有力工具。此外，我们还鉴定并分析了作为HCC分子标志物的NDS中的关键基因RTN3的可行性。 版权所有 © 2023 Gong, Chen, Liu and Cao.

The heterogeneity of tumor immune microenvironments is a major factor in poor prognosis among hepatocellular carcinoma (HCC) patients. Neutrophils have been identified as playing a critical role in the immune microenvironment of HCC based on recent single-cell studies. However, there is still a need to stratify HCC patients based on neutrophil heterogeneity. Therefore, developing an approach that efficiently describes "neutrophil characteristics" in HCC patients is crucial to guide clinical decision-making.We stratified two cohorts of HCC patients into molecular subtypes associated with neutrophils using bulk-sequencing and single-cell sequencing data. Additionally, we constructed a new risk model by integrating machine learning analysis from 101 prediction models. We compared the biological and molecular features among patient subgroups to assess the model's effectiveness. Furthermore, an essential gene identified in this study was validated through molecular biology experiments.We stratified patients with HCC into subtypes that exhibited significant differences in prognosis, clinical pathological characteristics, inflammation-related pathways, levels of immune infiltration, and expression levels of immune genes. Furthermore, A risk model called the "neutrophil-derived signature" (NDS) was constructed using machine learning, consisting of 10 essential genes. The NDS's RiskScore demonstrated superior accuracy to clinical variables and correlated with higher malignancy degrees. RiskScore was an independent prognostic factor for overall survival and showed predictive value for HCC patient prognosis. Additionally, we observed associations between RiskScore and the efficacy of immune therapy and chemotherapy drugs.Our study highlights the critical role of neutrophils in the tumor microenvironment of HCC. The developed NDS is a powerful tool for assessing the risk and clinical treatment of HCC. Furthermore, we identified and analyzed the feasibility of the critical gene RTN3 in NDS as a molecular marker for HCC.Copyright © 2023 Gong, Chen, Liu and Cao.