An angiogenic tumor phenotype predicts poor prognosis in ovarian cancer

Verena Wieser; Irina Tsibulak; Daniel Uwe Reimer; Alain Gustave Zeimet; Heidelinde Fiegl; Hubert Hackl; Christian Marth

doi:10.1016/j.ygyno.2023.01.034

An angiogenic tumor phenotype predicts poor prognosis in ovarian cancer

Gynecol Oncol. 2023 Mar:170:290-299. doi: 10.1016/j.ygyno.2023.01.034. Epub 2023 Feb 7.

Authors

Verena Wieser¹, Irina Tsibulak², Daniel Uwe Reimer², Alain Gustave Zeimet², Heidelinde Fiegl², Hubert Hackl³, Christian Marth²

Affiliations

¹ Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria. Electronic address: verena.wieser@i-med.ac.at.
² Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
³ Biocenter, Institute of Bioinformatics, Medical University Innsbruck, 6020 Innsbruck, Austria.

PMID: 36758419
DOI: 10.1016/j.ygyno.2023.01.034

Abstract

Objective: Epithelial ovarian cancer (OC) is the deadliest gynecological malignancy worldwide. Blocking angiogenesis 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 corroborated in an independent publicly available cohort from The Cancer Genome Atlas (TCGA, n = 582) and prediction 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 cohort (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 predictors 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 established score could be used to identify patients who respond to targeted angiogenic therapies, a concept that warrants prospective controlled clinical trials.

Keywords: Angiogenesis; Bevacizumab; Ovarian cancer; Tyrosine kinase inhibitor; VEGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / therapeutic use
Bevacizumab / therapeutic use
Female
Humans
Neovascularization, Pathologic / drug therapy
Ovarian Neoplasms* / drug therapy
Prognosis
Prospective Studies
Retrospective Studies
Vascular Endothelial Growth Factor A*

Substances

Bevacizumab
Vascular Endothelial Growth Factor A
Angiogenesis Inhibitors