Yang Jinyu, Wu Wangxi, Tang Xiaoli
Queen Mary School, Nanchang University, Nanchang 330031, China.
School of Basic Medical Sciences, Nanchang University, Nanchang 330031, China.
Biology (Basel). 2025 Apr 28;14(5):486. doi: 10.3390/biology14050486.
Endothelial cells (ECs) are critical drivers of tumour progression, and their angiogenic process has been widely studied. However, the post-angiogenic transition of tip endothelial cells after sprouting remains insufficiently characterised. In this study, we utilised single-cell RNA sequencing analyses to identify a novel EC transition signature associated with endothelial permeability, migration, metabolism, and vascular maturation. Within the transition pathway, we discovered a critical EC subpopulation, termed tip-to-capillary ECs (TC-ECs), that was enriched in tumour tissues. Comparative analyses of TC-ECs with tip and capillary ECs revealed distinct differences in pathway activity, cellular communication, and transcription factor activity. The EC transition signature demonstrated substantial prognostic significance, validated across multiple cancer cohorts from TCGA data, particularly in bladder cancer. Subsequently, we constructed a robust prognostic model for bladder cancer by integrating the EC transition signature with multiple machine-learning techniques. Compared with 31 existing models across the TCGA-BLCA, GSE32894, GSE32548, and GSE70691 cohorts, our model exhibited superior predictive performance. Stratification analysis identified significant differences between different risk groups regarding pathway activity, cellular infiltration, and therapeutic sensitivity. In conclusion, our comprehensive investigation identified a novel EC transition signature and developed a prognostic model for patient stratification, offering new insights into endothelial heterogeneity, angiogenesis regulation, and precision medicine.
内皮细胞（ECs）是肿瘤进展的关键驱动因素，其血管生成过程已得到广泛研究。然而，发芽后顶端内皮细胞的血管生成后转变仍未得到充分表征。在本研究中，我们利用单细胞RNA测序分析来识别一种与内皮通透性、迁移、代谢和血管成熟相关的新型EC转变特征。在转变途径中，我们发现了一个关键的EC亚群，称为顶端到毛细血管内皮细胞（TC-ECs），其在肿瘤组织中富集。对TC-ECs与顶端和毛细血管内皮细胞的比较分析揭示了途径活性、细胞通讯和转录因子活性方面的明显差异。EC转变特征显示出显著的预后意义，在来自TCGA数据的多个癌症队列中得到验证，尤其是在膀胱癌中。随后，我们通过将EC转变特征与多种机器学习技术相结合，构建了一个强大的膀胱癌预后模型。与TCGA-BLCA、GSE32894、GSE32548和GSE70691队列中的31个现有模型相比，我们的模型表现出卓越的预测性能。分层分析确定了不同风险组在途径活性、细胞浸润和治疗敏感性方面的显著差异。总之，我们的综合研究识别了一种新型EC转变特征，并开发了一个用于患者分层的预后模型，为内皮细胞异质性、血管生成调节和精准医学提供了新的见解。
