Open AccessThe Development of an Angiogenic Protein “Signature” in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling
Author(s) -
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,
Efthymios Kostouros,
E. Terpos,
Aristotelis Chatziioannou,
Meletios Α. Dimopoulos,
Aristotelis Bamias
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0156403
Subject(s) - ovarian cancer , ascites , angiogenesis , medicine , cancer research , oncology , serous ovarian cancer , profiling (computer programming) , bioinformatics , biology , pathology , computational biology , cancer , computer science , operating system
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 1 st -line carboplatin-based chemotherapy- were analyzed using the Proteome Profiler TM 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.