Bioinformatics Analysis and Experimental Verification Define Different Angiogenesis Subtypes in Endometrial Carcinoma and Identify a Prognostic Signature

Increasing evidence
indicates that peripheral blood vessels
play
a pivotal role in regulating tumor growth with the presence of new
blood vessels facilitating tumor growth and metastasis. Nevertheless,
the impact of specific molecule-mediated angiogenesis on the tumor
immune microenvironment (TIME) and individual prognosis of uterine
corpus endometrial carcinoma (UCEC) remains uncertain. The transcriptome
information on 217 prognostic angiogenesis-related genes was integrated,
and the angiogenesis patterns of 506 UCEC patients in The Cancer Genome
Atlas (TCGA) cohort were comprehensively evaluated. We identified
five angiogenic subtypes, namely, EC1, EC2, EC3, EC4, and EC5, which
differed significantly in terms of prognosis, clinicopathological
features, cancer hallmarks, genomic mutations, TIME patterns, and
immunotherapy responses. Additionally, an angiogenesis-related prognostic
risk score (APRS) was constructed to enable an individualized comprehensive
evaluation. In multiple cohorts, APRS demonstrated a powerful predictive
ability for the prognosis of UCEC patients. Likewise, APRS was confirmed
to be associated with clinicopathological features, genomic mutations,
cancer hallmarks, and TIME patterns in UCEC patients. The predictability
of APRS for immune checkpoint inhibitor (ICI) therapy was also salient.
Subsequently, the expression levels of four angiogenesis-related hub
genes were verified by qRT-PCR, immunohistochemistry, and single-cell
sequencing data analysis. The effects of four representative genes
on angiogenesis were validated by Wound-Healing and Transwell assays,
tube formation assay in vitro, and tumor xenograft model in vivo.
This study proffered a new classification of UCEC patients based on
angiogenesis. The established APRS may contribute to individualized
prognosis prediction and immunotherapy selections that are better
suited for UCEC patients.