Integrative analysis and experiments to explore GAS1 as a prognostic target for ovarian cancer based on angiogenesis-related genes

Background Intra-tumoral angiogenesis is vital for the proliferation and metastasis of ovarian cancer (OV). This study was to analyze the relationship of angiogenesis-related genes between clinical outcomes, immune landscape and immunotherapy in OV. Methods Combining the OV transcriptomic data from the GEO and TCGA databases, we identified the prognostic significance of angiogenesis-related genes and angiogenesis subtypes through unsupervised clustering analysis. Analyses of clinical significance, functional pathways and immune infiltration were performed on subtypes accordingly. The angiogenesis-based risk score(ARG_score) was then constructed and the link between the risk score and clinicopathological parameters, immune landscapes, and genomic mutations were further analyzed. Finally, we validated the function of one angiogenesis-related gene using ovarian cancer cell lines. Results Using consensus clustering, we developed two new angiogenesis subtypes with significant differences in clinicopathological features, prognostic outcomes and tumor microenvironment (TME) characteristics. Patients from high- and low-ARG_score groups showed a distinct divergence among clinical prognosis, infiltration of immune cells, immune checkpoint gene expression level, and chemotherapeutic drug sensitivity. Additionally, the hub prognostic genes GAS1 was abnormally expressed in OV tissues, and in vitro functional assays revealed that upregulation of GAS1 effectively suppressed the proliferation and migration of OV cells. Conclusions Our findings highlighted the inseparable relationship between angiogenesis and immune in OV microenvironment and GAS1 may as a potential diagnostic and prognostic biomarker for OV patients.