Tregs are involved in VEGFA/ VASH1-related angiogenesis pathway in ovarian cancer

Sijing Qiao1, Yue Hou1, Qing Rong1

  • 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People's Republic of China; College of Medicine, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China; Key Laboratory of Gynecology Oncology of Shandong Province, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People's Republic of China; Shandong Engineering Laboratory for Urogynecology; Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.

Insights

Regulatory T cells (Tregs) may influence ovarian cancer (OC) angiogenesis via vasohibin1 (VASH1) and vascular endothelial growth factor A (VEGFA). This suggests new therapeutic strategies combining anti-angiogenic and immunotherapy for OC treatment.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Anti-angiogenic therapy targeting vascular endothelial growth factor A (VEGFA) is a standard treatment for advanced ovarian cancer (OC), but faces challenges like adverse effects and resistance.
  • Regulatory T cells (Tregs) are key players in tumor immune escape and can influence VEGFA function within the tumor microenvironment (TME).
  • The specific roles of vasohibin1 (VASH1) and Tregs in OC angiogenesis and their interplay within the TME remain largely unexplored.

Purpose of the Study:

  • To investigate the relationship between angiogenesis and immunosuppression in the TME of OC.
  • To validate the association of VEGFA and VASH1 with angiogenesis and their prognostic significance in OC.
  • To explore the correlation between Treg infiltration, specifically forkhead box protein 3 (FOXP3) expression, and angiogenesis-related molecules in OC.

Main Methods:

  • Analysis of VEGFA and VASH1 expression in relation to clinicopathological features, microvessel density, and patient prognosis in OC.
  • Assessment of Treg infiltration (FOXP3+) and its correlation with angiogenesis markers.
  • Gene set enrichment analysis (GSEA) to identify common signaling pathways involving VEGFA, VASH1, and Tregs in OC development.

Main Results:

  • VEGFA and VASH1 expression levels were significantly associated with advanced clinicopathological stage, increased microvessel density, and poorer prognosis in OC patients.
  • A positive correlation was observed between VEGFA and VASH1 expression, both linked to pro-angiogenic pathways.
  • High FOXP3 expression in Tregs correlated with angiogenesis-related molecules and was associated with unfavorable patient outcomes.

Conclusions:

  • VEGFA and VASH1 are important prognostic factors in OC and are implicated in tumor angiogenesis.
  • Tregs may contribute to OC progression by regulating tumor angiogenesis through VEGFA and VASH1.
  • These findings highlight potential synergistic therapeutic strategies for OC, combining anti-angiogenic treatments with immunotherapy targeting Tregs.

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