PLoS ONE (Jan 2016)

The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling.

  • Sofia-Paraskevi Trachana,
  • Eleftherios Pilalis,
  • Nikos G Gavalas,
  • Kimon Tzannis,
  • Olga Papadodima,
  • Michalis Liontos,
  • Alexandros Rodolakis,
  • Georgios Vlachos,
  • Nikolaos Thomakos,
  • Dimitrios Haidopoulos,
  • Maria Lykka,
  • Konstantinos Koutsoukos,
  • Efthimios Kostouros,
  • Evagelos Terpos,
  • Aristotelis Chatziioannou,
  • Meletios-Athanasios Dimopoulos,
  • Aristotelis Bamias

DOI
https://doi.org/10.1371/journal.pone.0156403
Journal volume & issue
Vol. 11, no. 6
p. e0156403

Abstract

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Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001) and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001). This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF) in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies.