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Serum Vascular Endothelial Growth Factor-A as a Prognostic Biomarker for Epithelial Ovarian Cancer
  1. Hiroaki Komatsu, MD*,
  2. Tetsuro Oishi, MD, PhD*,
  3. Hiroaki Itamochi, MD, PhD,
  4. Muneaki Shimada, MD, PhD*,
  5. Shinya Sato, MD, PhD*,
  6. Jun Chikumi, MD, PhD*,
  7. Seiya Sato, MD, PhD,
  8. Michiko Nonaka, MD, PhD*,
  9. Mayumi Sawada, MD*,
  10. Makoto Wakahara, MD,
  11. Yoshihisa Umekita, MD, PhD and
  12. Tasuku Harada, MD, PhD*
  1. * Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago;
  2. Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Morioka; and
  3. Department of Pathology, Tottori University School of Medicine, Yonago, Japan.
  1. Address correspondence and reprint requests to Tetsuro Oishi, MD, PhD, Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36–1 Nishicho, Yonago, Tottori Prefecture, 683–8504, Japan. E-mail: tetsuro{at}


Background Bevacizumab, which targets vascular endothelial growth factor (VEGF)-A, has recently been proven to be effective for the treatment of epithelial ovarian cancer (EOC). Thus, interest in VEGF-A has increased. There are few reports on concomitant detection of both ligands and its soluble receptors in serum samples, and the significance of serum VEGF-A in EOC is unclear, unlike the situation with tissue samples. We conducted the present study to explore the levels of serum VEGF family and its receptors and to evaluate their utility as prognostic biomarkers.

Methods A total of 128 patients with EOC, who were consecutively treated at Tottori University Hospital between 2006 and 2012, were included. Blood samples were collected before initial surgery. Serum concentrations of VEGF-A, VEGF-C, VEGFR-1, and VEGFR-2 were analyzed by enzyme-linked immunosorbent assay. We also examined the mRNA and protein expression of VEGF-A in tumor tissue from 30 cases by real-time reverse transcription polymerase chain reaction and immunohistochemistry.

Results The levels of VEGF-A in patients with stage III/IV disease were significantly higher than those with stage I/II disease (P = 0.0036). On the other hand, the level of VEGFR-2 in stage III/IV was significantly lower than that in stage I/II (P = 0.0026). With the cutoff value of VEGF/VEGFRs at the median level, the overall survival (OS) for patients with high VEGF-A levels was significantly lower than those with low levels (P = 0.015). Patients with high VEGFR-2 levels showed better prognosis than those with low VEGFR-2 levels (P = 0.023). Multivariate analysis revealed that International Federation of Gynecology and Obstetrics stage and serum VEGF-A were independent prognostic factors for OS [hazard ratio 2.01, 95% confidence interval (1.13–3.63), P = 0.017]. There was no significant correlation between mRNA or protein expression and serum levels of VEGF-A.

Conclusions Serum VEGF-A is an independent prognostic factor for OS in patients with EOC, implying that serum VEGF-A is a prognostic biomarker for EOC. Further study to validate the data is needed.

  • VEGF
  • Biomarker
  • Angiogenesis
  • Ovarian cancer

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  • The authors declare no conflicts of interest.