鉴于人们对肝细胞癌（HCC）和门静脉癌栓（PVTT）的代谢异质性越来越感兴趣。本研究利用多组学组合全面分析了 HCC、PVTT 和正常肝脏样本的代谢异质性。获得了包含六种主要细胞类型的单细胞 RNA 测序数据集用于集成分析。使用聚类分层确定最佳亚型，并使用空间转录组学和荧光多重免疫组织化学进行验证。然后，使用公共队列的多组学数据计算基于组合指数的元簇，以验证其预后意义。我们的研究首先在多组学水平上描绘了 HCC 和 PVTT 中非恶性细胞的代谢异质性景观。最佳亚型解释了 PVTT 形成和发展的代谢特征。组合指数提供了预后和免疫治疗反应的有效预测。综合指数较高的患者预后相对较差(p <0.001)。我们还发现多胺代谢是参与 HCC 和 PVTT 代谢异质性转化的关键代谢途径，并确定与正常组织相比，ODC1 在 PVTT 中的表达显着较高（p = 0.03）。我们的研究结果揭示了 HCC 和 PVTT 中非恶性细胞代谢的一致性和异质性。基于癌症相关成纤维细胞和骨髓细胞的风险分层有助于预测预后并指导治疗。这为理解疾病发展和免疫治疗反应提供了新的方向。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Given the growing interest in the metabolic heterogeneity of hepatocellular carcinoma (HCC) and portal vein tumour thrombus (PVTT). This study comprehensively analysed the metabolic heterogeneity of HCC, PVTT, and normal liver samples using multi-omics combinations. A single-cell RNA sequencing dataset encompassing six major cell types was obtained for integrated analysis. The optimal subtypes were identified using cluster stratification and validated using spatial transcriptomics and fluorescent multiplex immunohistochemistry. Then, a combined index based meta-cluster was calculated to verify its prognostic significance using multi-omics data from public cohorts. Our study first depicted the metabolic heterogeneity landscape of non-malignant cells in HCC and PVTT at multiomics levels. The optimal subtypes interpret the metabolic characteristics of PVTT formation and development. The combined index provided effective predictions of prognosis and immunotherapy responses. Patients with a higher combined index had a relatively poor prognosis (p <0.001). We also found metabolism of polyamines was a key metabolic pathway involved in conversion of metabolic heterogeneity in HCC and PVTT, and identified ODC1 was significantly higher expressed in PVTT compared to normal tissue (p =0.03). Our findings revealed both consistency and heterogeneity in the metabolism of non-malignant cells in HCC and PVTT. The risk stratification based on cancer-associated fibroblasts and myeloid cells conduce to predict prognosis and guide treatment. This offers new directions for understanding disease development and immunotherapy responses.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.