ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1431624
A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma
Provisionally accepted
- 1First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- 2Fujian Institute of Abdominal Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
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Objective Hepatocellular carcinoma (HCC) is the most common type of liver cancer with poor prognosis. Vasculogenic mimicry (VM) is an angiogenetic process associated with the growth and spread of malignant tumors. We aim to create a VM related genes-based prediction model to evaluate the prognosis and immune infiltration in HCC patients. Materials and methods 364 patients from the TCGA database and 242 patients from the GEO database were enrolled in this study with completed clinical information and transcriptome sequencing data. LASSO-COX regression analysis was performed to identify VM-related hub genes. Biological process (BP), Kyoto Encyclopedia of Genes and Genomes Enrichment Analysis (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses were applied to analyze the biological function of the hub genes. The related-gene signature's predictive significance was confirmed in GSE14520 cohort. Rt-PCR and CD31/E-cadherin immunofluorescence staining were applied to elucidate that the VM score can reflect the vasculogenic mimicry of tumor. Results This study found that VM-related genes were enriched in proteoglycans in cancer pathway and VEGF signaling pathway. A predictive signature based on 5 genes (MAPK3, MAPK1, VEGFA, NOTCH1 and TGFB1) was deemed to an independent risk factor for the prognosis of HCC patients. GSEA analysis revealed that genes positively correlated with the signature were enriched in the “Notch signaling pathway” which activated in angiogenesis. Additionally, CIBERSORTx analysis showed that higher expression of the VM score was associated with immune infiltration of naive CD4+ T cell in HCC. Pearson correlation analysis revealed a positive link between increased of the VM score and inhibitory immunological checkpoints (HVEM and PD-1). Furthermore, in vivo experiments have confirmed that the VM score can effectively reflect the degree of vasculogenic mimicry in hepatocellular carcinoma tissue. The nomogram that utilized the VM score and TNM stage to predict the individual survival probability of HCC patients was satisfactory. Conclusion The VM score and nomogram constructed to predict survival probability of HCC patients achieved satisfactory outcomes in this study. The relationship between the biological function of the VM score and immune infiltration could potentially serve as a target for tumor therapy in liver cancer.
Keywords: Hepatocellular Carcinoma, Vasculogenic mimicry, Immune infiltration, immune checkpoints, Prognosis prediction
Received: 24 May 2024; Accepted: 02 Jun 2025.
Copyright: © 2025 Zhong, Fadian, Zhang, Zhang, Zhang and Weng. 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:
Xiang Zhang, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
Shangeng Weng, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
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