An angiogenic tumor phenotype predicts poor prognosis in ovarian cancer

Objective. Epithelial ovarian cancer (OC) is the deadliest gynecological malignancy worldwide. Blocking an-giogenesis with bevacizumab, an antibody targeting vascular endothelial growth factor (VEGF), shows efficacy in different lines of OC therapy. This study investigates the clinical impact of tumoral expression of angiogenesis-related genes and their association with bevacizumab response in OC in retrospective analysis of three independent cohorts.Methods. mRNA expression of seven angiogenic genes (VEGF, VEGFR2, PDGFA, PDGFB, PDGFRA, PDGFRB, KIT) was quantified in an inception OC cohort (n = 195) and a transcriptional tumor angiogenesis score from 0 to 3 was established and linked to progression-free survival (PFS) and overall survival (OS). This score was corrob-orated in an independent publicly available cohort from The Cancer Genome Atlas (TCGA, n = 582) and predic-tion of therapeutic efficacy of bevacizumab by the angiogenesis score was analyzed in the Gene Expression Omnibus (GEO) dataset GSE140082 (n = 380) from the ICON7-trial.Results. The tumor angiogenesis score prognosticated PFS and OS in patients with OC from the inception co-hort (p < 0.001, respectively). Tumoral PDGFA expression (PFS: HR 2.46, p = 0.005; OS: HR 2.26, p = 0.011) and a high tumoral transcriptional angiogenesis score (PFS: HR 1.41, p = 0.018) were identified as independent predic-tors of clinical outcome. The transcriptional angiogenesis score exhibited a significant though smaller effect size on PFS in the TCGA cohort. However, in the ICON7-trial, the angiogenesis score was not associated with benefit of bevacizumab treatment.Conclusions. Our study indicates that tumoral expression of angiogenic genes is unfavorable in OC. The estab-lished score could be used to identify patients who respond to targeted angiogenic therapies, a concept that war-rants prospective controlled clinical trials.(c) 2023 The Authors. Published by Elsevier Inc.his is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Automated summary

This study investigated the expression of angiogenesis-related genes in ovarian cancer and their association with the response to bevacizumab therapy. The findings suggest that tumoral expression of PDGFA and a high transcriptional angiogenesis score are independent predictors of clinical outcome in ovarian cancer patients.