VEGF-C serum level is associated with response to bevacizumab maintenance therapy in primary ovarian cancer patients

PLoS One. 2022 Jun 10;17(6):e0269680. doi: 10.1371/journal.pone.0269680. eCollection 2022.

Abstract

Objective: At present, maintenance therapy with the antiangiogenic agent bevacizumab or with PARP-inhibitors represent two options for BRCA-wildtype ovarian cancer patients, after platinum-based first line chemotherapy. The identification of molecular markers to predict patient response to different maintenance therapies remains a major challenge. In the present study we analyzed the predictive potential of vascular endothelial growth factor C (VEGF-C) to identify ovarian cancer patients that might benefit from an antiangiogenic therapy.

Methods: 101 patients with primary epithelial ovarian cancer were analyzed for serum levels of VEGF-A,-C and CA-125 by ELISA. Serum levels were compared between patients with low pT-stage (pT1a-pT2c n = 11), healthy individuals (n = 27) and patients with higher pT-stage (> = pT3 n = 90). Adjusted ROC curves and an adjusted logistic regression model were carried out to evaluate the potential impact of VEGF-A and -C, as well as CA-125 serum level concentration on bevacizumab-therapy response, under consideration of covariates such as FIGO, pM, pN and residual tumor after surgery.

Results: A patient which has in comparison twice the VEGF-C concentration in serum, has a significant increased chance of response to bevacizumab by a factor of 2.79. Further, only VEGF-C serum levels were significantly higher in the group of patients with lower pT-stage compared to healthy individuals, whereas VEGF-A or CA-125 serum levels could not discriminate between healthy individuals and patients with ovarian cancer at low pT-stages.

Conclusion: VEGF-C serum level might serve as as a biomarker to evaluate treatment response under bevacizumab.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Bevacizumab / therapeutic use
  • CA-125 Antigen
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Female
  • Humans
  • Ovarian Neoplasms* / pathology
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor C*

Substances

  • Angiogenesis Inhibitors
  • CA-125 Antigen
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Bevacizumab

Grants and funding

The author(s) received no specific funding for this work.