Abstract
BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in males; we aim to establish a novel angiogenesis-related gene signature for biochemical recurrence (BCR) prediction in PCa patients following radical therapy. METHODS: Gene expression profiles and corresponding clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We quantified the levels of various cancer hallmarks and identified angiogenesis as the primary risk factor for BCR. Then machine learning methods combined with Cox regression analysis were used to screen prognostic genes and construct an angiogenesis-related gene signature, which was further verified in external cohorts. Furthermore, estimation of immune cell abundance and prediction of drug responses were also conducted to detect potential mechanisms. RESULTS: Angiogenesis was regarded as the leading risk factor for BCR in PCa patients (HR = 1.58, 95% CI: 1.38-1.81), and a novel prognostic signature based on three genes (NRP1, JAG2, and VCAN) was developed in the training cohort and successfully validated in another three independent cohorts. In all datasets, this signature was identified as a prognostic factor with promising and robust predictive values. Moreover, it also predicted higher infiltration of regulatory T cells and M2-polarized macrophages and increased drug sensitivity of angiogenesis inhibitors in high-risk patients. CONCLUSIONS: The angiogenesis-related three-gene signature may serve as an independent prognostic factor for BCR, which would contribute to risk stratification and personalized management of PCa patients after radical therapy in clinical practice.