Abstract C121: Single-cell RNA profiling reveals metastatic capacity of the malignant cells underlying microvascular invasion in patients with hepatocellular carcinoma

Abstract Microvascular invasion (MVI) refers to the infiltration of tumor cells into blood vessels in hepatocellular carcinoma (HCC). This phenomenon is the main route of intrahepatic metastasis leading to increased recurrence and poor prognosis in patients with HCC. Here, we performed single-cell RNA sequencing analysis to investigate the cellular interactions between malignant and endothelial cells in patients with MVI-positive (MVIP) HCC compared to MVI-negative (MVIN). Malignant cells from MVIP patients showed enrichment of DNA replication and cell cycle signaling pathways, while pathways-associated with focal adhesion and the extracellular matrix were significantly downregulated compared to MVIN patients. These features might facilitate rapid progression and metastasis. Endothelial cells in MVIP patients exhibited upregulation of angiogenesis-related genes and transcription factor activity, indicating that pro-angiogenic state promotes tumor cell invasion and dissemination. Cell–cell interaction analysis revealed cancer invasion in MVIP patient might be due to strong interaction between the angiogenic factor in endothelial cell and tumor-associated transmembrane proteoglycans in malignant cell. In summary, our single-cell analysis suggests that malignant cells with high expression of transmembrane proteoglycans may rapidly proliferate and infiltrate into endothelial cells expressing high level of angiogenic factor resulting in inferior outcomes in MVIP patients. Citation Format: Yeseong Hwang, Chae Min Lee, Haeryoung Kim, Sungsoon Fang, Yong-ho Lee. Single-cell RNA profiling reveals metastatic capacity of the malignant cells underlying microvascular invasion in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C121.