The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling.
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.
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Sofia-Paraskevi
SP
Trachana
Metabolic Engineering and Bioinformatics Program Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Eleftherios
E
Pilalis
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Nikos G
NG
Gavalas
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Kimon
K
Tzannis
Metabolic Engineering and Bioinformatics Program Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Olga
O
Papadodima
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Michalis
M
Liontos
First Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Alexandros
A
Rodolakis
First Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Georgios
G
Vlachos
First Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Nikolaos
N
Thomakos
First Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Dimitrios
D
Haidopoulos
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Maria
M
Lykka
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Konstantinos
K
Koutsoukos
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Efthimios
E
Kostouros
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Evagelos
E
Terpos
Metabolic Engineering and Bioinformatics Program Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Aristotelis
A
Chatziioannou
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Meletios-Athanasios
MA
Dimopoulos
Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.
Aristotelis
A
Bamias
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001201:Ascites / Q000378:metabolism; D001202:Ascitic Fluid / Q000378:metabolism; D016190:Carboplatin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D010984:Platinum / Q000627:therapeutic use; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D010984:Platinum; D016190:Carboplatin