A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma
ObjectiveHepatocellular carcinoma (HCC) is the most common type of liver cancer and has a poor prognosis. Vasculogenic mimicry (VM) is an angiogenic process associated with the growth and spread of malignant tumors. In this study, we aim to create a VM-related, gene-based prediction model to evaluat...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1431624/full |
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| author | Yun Zhong Yun Zhong Yun Zhong Yun Zhong Fadian Ding Fadian Ding Fadian Ding Fadian Ding Han Zhang Han Zhang Han Zhang Han Zhang Denghan Zhang Denghan Zhang Denghan Zhang Denghan Zhang Xiang Zhang Xiang Zhang Xiang Zhang Xiang Zhang Shangeng Weng Shangeng Weng Shangeng Weng Shangeng Weng |
| author_facet | Yun Zhong Yun Zhong Yun Zhong Yun Zhong Fadian Ding Fadian Ding Fadian Ding Fadian Ding Han Zhang Han Zhang Han Zhang Han Zhang Denghan Zhang Denghan Zhang Denghan Zhang Denghan Zhang Xiang Zhang Xiang Zhang Xiang Zhang Xiang Zhang Shangeng Weng Shangeng Weng Shangeng Weng Shangeng Weng |
| author_sort | Yun Zhong |
| collection | DOAJ |
| description | ObjectiveHepatocellular carcinoma (HCC) is the most common type of liver cancer and has a poor prognosis. Vasculogenic mimicry (VM) is an angiogenic process associated with the growth and spread of malignant tumors. In this study, we aim to create a VM-related, gene-based prediction model to evaluate the prognosis and immune infiltration in HCC patients.Materials and methodsA total of 364 patients from the TCGA database and 242 patients from the GEO database with complete clinical information and transcriptome sequencing data were enrolled in this study. LASSO Cox regression analysis was performed to identify VM-related hub genes. Biological process (BP), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and gene set enrichment analysis (GSEA) were applied to analyze the biological function of the hub genes. The predictive significance of the related gene signature was confirmed in the GSE14520 cohort. RT-PCR and CD31/E-cadherin immunofluorescence staining were applied to elucidate that the VM score can reflect the degree of vasculogenic mimicry within tumors.ResultsThis study found that VM-related genes were enriched in the proteoglycans in the cancer pathway and the VEGF signaling pathway. A predictive signature based on five genes (MAPK3, MAPK1, VEGFA, NOTCH1, and TGFB1) was identified as an independent risk factor for HCC patient prognosis. GSEA revealed that genes that positively correlated with the signature were enriched in the “NOTCH signaling pathway,” which is activated during angiogenesis. Additionally, CIBERSORTx analysis showed that higher expression of the VM score was associated with immune infiltration of naïve CD4+ T cells in HCC. Pearson correlation analysis revealed a positive link between an increased 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 survival probability of individual HCC patients was satisfactory.ConclusionThe VM score and nomogram constructed to predict the 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. |
| format | Article |
| id | doaj-art-8f688fee008942e49e23e8ba8d215e89 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-8f688fee008942e49e23e8ba8d215e892025-08-20T03:28:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.14316241431624A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinomaYun Zhong0Yun Zhong1Yun Zhong2Yun Zhong3Fadian Ding4Fadian Ding5Fadian Ding6Fadian Ding7Han Zhang8Han Zhang9Han Zhang10Han Zhang11Denghan Zhang12Denghan Zhang13Denghan Zhang14Denghan Zhang15Xiang Zhang16Xiang Zhang17Xiang Zhang18Xiang Zhang19Shangeng Weng20Shangeng Weng21Shangeng Weng22Shangeng Weng23Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaObjectiveHepatocellular carcinoma (HCC) is the most common type of liver cancer and has a poor prognosis. Vasculogenic mimicry (VM) is an angiogenic process associated with the growth and spread of malignant tumors. In this study, we aim to create a VM-related, gene-based prediction model to evaluate the prognosis and immune infiltration in HCC patients.Materials and methodsA total of 364 patients from the TCGA database and 242 patients from the GEO database with complete clinical information and transcriptome sequencing data were enrolled in this study. LASSO Cox regression analysis was performed to identify VM-related hub genes. Biological process (BP), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and gene set enrichment analysis (GSEA) were applied to analyze the biological function of the hub genes. The predictive significance of the related gene signature was confirmed in the GSE14520 cohort. RT-PCR and CD31/E-cadherin immunofluorescence staining were applied to elucidate that the VM score can reflect the degree of vasculogenic mimicry within tumors.ResultsThis study found that VM-related genes were enriched in the proteoglycans in the cancer pathway and the VEGF signaling pathway. A predictive signature based on five genes (MAPK3, MAPK1, VEGFA, NOTCH1, and TGFB1) was identified as an independent risk factor for HCC patient prognosis. GSEA revealed that genes that positively correlated with the signature were enriched in the “NOTCH signaling pathway,” which is activated during angiogenesis. Additionally, CIBERSORTx analysis showed that higher expression of the VM score was associated with immune infiltration of naïve CD4+ T cells in HCC. Pearson correlation analysis revealed a positive link between an increased 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 survival probability of individual HCC patients was satisfactory.ConclusionThe VM score and nomogram constructed to predict the 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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1431624/fullhepatocellular carcinomavasculogenic mimicryimmune infiltrationimmune checkpointsprognosis prediction |
| spellingShingle | Yun Zhong Yun Zhong Yun Zhong Yun Zhong Fadian Ding Fadian Ding Fadian Ding Fadian Ding Han Zhang Han Zhang Han Zhang Han Zhang Denghan Zhang Denghan Zhang Denghan Zhang Denghan Zhang Xiang Zhang Xiang Zhang Xiang Zhang Xiang Zhang Shangeng Weng Shangeng Weng Shangeng Weng Shangeng Weng A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma Frontiers in Genetics hepatocellular carcinoma vasculogenic mimicry immune infiltration immune checkpoints prognosis prediction |
| title | A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma |
| title_full | A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma |
| title_fullStr | A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma |
| title_full_unstemmed | A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma |
| title_short | A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma |
| title_sort | novel vasculogenic mimicry related nomogram predicts prognosis in hepatocellular carcinoma |
| topic | hepatocellular carcinoma vasculogenic mimicry immune infiltration immune checkpoints prognosis prediction |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1431624/full |
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