Vascular endothelial growth factor receptor-2 and its association with tumor immune regulatory gene expression in...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Anti-vascular endothelial growth factor (anti-VEGF) drugs were the primary treatment for advanced hepatocellular carcinoma (HCC).
• Recent studies show combination therapy with bevacizumab (anti-VEGF) and atezolizumab (immune checkpoint blockade) surpasses sorafenib in efficacy.
• The intricate relationship between VEGF signaling and the tumor immune microenvironment (TME) in HCC remains unclear.

Purpose of the Study:

• To investigate the correlation between the VEGF signaling pathway and the TME in HCC.
• To analyze immune cell infiltration, immune markers, genomic instability, and immune-related pathways in relation to VEGF signaling.
• To explore the prognostic implications of VEGF signaling and immune cell activation in HCC.

Main Methods:

• Analysis of RNA sequencing and clinical data from 365 HCC patients from The Cancer Genome Atlas (TCGA).
• Calculation of VEGF signaling pathway scores.
• Enrichment analysis of differentially expressed genes between VEGF score subtypes.

Main Results:

• A positive correlation was observed between VEGF signaling pathway scores and immune cell infiltration.
• VEGF signaling pathway scores were also positively correlated with the expression of 66 immune markers.
• Genes differentially expressed between VEGF subtypes were enriched in immune-related Gene Ontology terms.
• Both VEGF signaling and activated CD8+ T cells showed a positive correlation with patient prognosis.

Conclusions:

• VEGF signaling pathway and the tumor immune microenvironment are co-activated in HCC.
• This co-activation provides mechanistic insight into the efficacy of combination therapies involving anti-VEGF agents and immune checkpoint inhibitors.
• Targeting both VEGF signaling and immune activation may represent a promising therapeutic strategy for HCC.