Angiogenic Edge of ANGPT2: Genetic Variants Shape Prostate Cancer Prognosis on Androgen Deprivation Therapy

Prostate cancer, a leading global malignancy, exhibits variable progression influenced by angiogenesis, the formation of new blood vessels critical for tumor growth and metastasis. We investigated the impact of genetic variants of angiogenesis-related genes on the survival outcomes of patients with prostate cancer receiving androgen deprivation therapy (ADT).

We conducted a genetic association study of 87 single-nucleotide polymorphisms across seven angiogenic genes in 630 patients with prostate cancer undergoing ADT. Survival analysis was used to assess progression-free survival (PFS) and overall survival (OS). Functional analyses, including gene ontology and pathway enrichment, were performed to elucidate the underlying biological mechanisms.

ANGPT2 rs2959822 was significantly associated with PFS [hazard ratio (HR)=1.22, p=0.015] and OS (HR=1.22, p=0.021). The minor allele A increased the risk of disease progression and mortality. Functional analyses revealed that rs2959822 influenced ANGPT2 expression. Elevated ANGPT2 expression was correlated with higher Gleason score, advanced tumor stage, and shorter PFS. Gene set enrichment analysis linked ANGPT2 to epithelial-mesenchymal transition (EMT), demonstrating positive correlations with several key EMT genes, along with increased immune cell infiltration, indicating its multifaceted oncogenic roles.

ANGPT2 rs2959822 influences the survival outcomes of patients with prostate cancer undergoing ADT. In addition to angiogenesis, ANGPT2 plays a critical role in prostate cancer progression by promoting EMT and modulating the tumor immune microenvironment.