World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 2, April 2025, pages 173-181

Angiogenesis Is Associated With Aggressive Biology That Counterbalances With Tumor Immunogenicity in Hepatocellular Carcinoma

Figures

↓  Figure 1. Intra-tumoral angiogenesis score correlates with the expression of VEGF (VEGFC)-, endothelial cell marker (CD31 and VWF)-, and vascular stability (TIE1 and 2, ANGPT1, VE-cadherin, CLDN5 and JAM2)-related genes in the TCGA and GSE76427 cohorts. High versus low, median angiogenesis pathway score. ANGPT1: angiopoietin 1; CD31/PECAM-1: platelet endothelial cell adhesion molecule; CLDN5: Claudin5; JAM2: junction adhesion molecule 2; TIE1 and 2: tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and 2; VE-cadherin/CD144: vascular endothelial cadherin; VEGF: vascular endothelial growth factor; VWF: von Willebrand factor.
Figure 1.
↓  Figure 2. Intra-tumoral angiogenesis score correlates with the presence of MEC and LEC in the TCGA and GSE76427 cohorts. High versus low, median angiogenesis pathway score. MEC: microvascular endothelial cell; LEC: lymphatic endothelial cell.
Figure 2.
↓  Figure 3. Intra-tumoral angiogenesis score does not correlate with OS or DFS in either the TCGA and GSE76427 cohorts. High versus low, median angiogenesis pathway score. DFS: disease-free survival; OS: overall survival.
Figure 3.
↓  Figure 4. Tumors with high intra-tumoral angiogenesis score demonstrate enrichment of pro-tumor gene sets in the TCGA and GSE76427 cohorts. GSEA with NES and FDR for glycolysis, Notch signaling, Hedgehog signaling, KRAS signaling, EMT, and TGF-β signaling. EMT: epithelial mesenchymal transition; FDR: false discovery rate; GSEA: Gene Set Enrichment Analysis; NES: normalized enrichment score; TGF-β: transforming growth factor-beta.
Figure 4.
↓  Figure 5. High angiogenesis score is associated with increased CYT in both the TCGA and GSE76427 cohorts, while pro-and anti-tumor infiltrating immune cells showed variable presence. (a) CD8 and Th1 infiltration was associated with low angiogenesis score while M1 macrophages and cDC infiltration was associated with high angiogenesis score. (b) CYT score was correlated with tumors which had high angiogenesis score. cDC: conventional dendritic cell; CYT: cytolytic activity.
Figure 5.
↓  Figure 6. Tumors with high intra-tumoral angiogenesis score demonstrate enrichment of inflammatory response gene sets in the TCGA and GSE76427 cohorts. GSEA with NES and FDR for inflammatory response, TNF-α, allograft rejection, INF-α and γ. FDR: false discovery rate; GSEA: Gene Set Enrichment Analysis; INF-α and γ: interferon-alpha and gamma; NES: normalized enrichment score; TNF-α: tumor necrosis factor-alpha.
Figure 6.
↓  Figure 7. Intra-tumoral angiogenesis score correlates with checkpoint marker expression in the TCGA and GSE76427 cohorts. High versus low, median angiogenesis pathway score. PD1: programmed cell death protein 1; PD-L1 and 2: programmed death ligand 1 and 2; CTLA-4/CD152: cytotoxic T lymphocyte-associated protein 4.
Figure 7.