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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 |
doi: 10.3389/fcell.2025.1449624
Single-cell sequencing reveals cell heterogeneity and aberrantly activated pathways associated with microvascular invasion in hepatocellular carcinoma
Provisionally accepted- The Second People's Hospital of Hefei, Hefei, China
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with microvascular invasion (MVI) identified as a major predictor of early recurrence. However, the intratumor cellular heterogeneity of MVI, the identification of pertinent biomarkers, and the role of intercellular signalling interactions in MVI progression are unclear. The present study utilized single-cell transcriptomic data from public datasingle-cell sequencing technology to conduct an in-depth transcriptome analysis of tumour tissues and adjacent nontumor tissues from five patients with hepatocellular carcinoma, focusing particularly on samples from three patients exhibiting microvascular invasion. The present findings indicated that MVI-positive malignant cells activate multiple signalling pathways to facilitate invasion and metastasis. Additionally, the present study identified specific malignant cell subtypes strongly associated with MVI. These subtypes exhibit distinctive gene expression patterns related to proliferation, invasion, and metabolic reprogramming of tumour cells. Further analysis revealed that the laminin and VEGF signalling pathways are crucial for remodelling of the tumour microenvironment and angiogenesis associated with MVI. Moreover, the MARCKSL1 gene is predominantly expressed in MVI-positive malignant cells, and this gene may contribute to the progression of MVI by interacting with the PTN signalling network. In addition, the MARCKSL1 gene is also linked to tumour resistance to multiple anticancer drugs. Overall, the present study shed light on the molecular characteristics and functional heterogeneity of MVI-associated malignant cell subpopulations. The single-cell transcriptome and bioinformatics analyses provided insights into the mechanisms driving MVI, thereby potentially aiding the development of targeted diagnostic and therapeutic strategies.Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, accounting for approximately 90% of all liver cancer cases [1]. Previous research has established microvascular invasion (MVI) as the strongest independent predictor of early recurrence in HCC patients [2,3]. However, the intratumor cellular heterogeneity of MVI, the identification of pertinent biomarkers, and the role of intercellular signalling interactions in MVI progression are unclear. The present study utilized single-cell sequencing technology to conduct an in-depth transcriptome analysis of tumour tissues and adjacent nontumor tissues from five patients with hepatocellular carcinoma, focusing particularly on samples from three patients exhibiting microvascular invasion.
Keywords: Single-cell RNA-sequencing, Hepatocellular Carcinoma, Microvascular invasion, MARCKSL1 gene, Prognostic signature
Received: 15 Jun 2024; Accepted: 15 Jan 2025.
Copyright: © 2025 Cui, Zeng, Tang and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shiwu Yin, The Second People's Hospital of Hefei, Hefei, China
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