Abstract
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.
Highlights
Ovarian cancer is the most lethal gynecological type of cancer in developed countries
We have previously shown that vascular endothelial growth factor (VEGF) levels are significantly higher in the ascites of women with advanced ovarian cancer compared to those in the serum of the same patients [11], suggesting that the angiogenic activity is most intense in the peritoneal cavity, the anatomical region of the highest disease burden
We found that a reduced marker set can form a promising tool, which is strongly associated with prognosis following cytoreductive surgery and standard cytotoxic chemotherapy
Summary
Ovarian cancer is the most lethal gynecological type of cancer in developed countries. According to SEER data, approximately 23000 women will be diagnosed with ovarian cancer in the forthcoming years and about 15000 of them will die of the disease [1]. Despite the initial effectiveness of this therapeutic approach, the majority of women will relapse, with a median PFS of around 18 months, and eventually die from ovarian cancer [3]. An expanding pipeline of targeted therapies and increased appreciation for the molecular drivers within ovarian cancers have spawned a number of novel approaches for detection and treatment monitoring; these approaches include primarily blood tests for circulating tumor cells, tumor-derived exosomes, stem/progenitor cells, soluble tumor markers, as well as the use of genomic or proteomic information [4,5,6,7,8]. There are still no reliable biomarkers capable of identifying ovarian cancer treatment failures before radiographic or biochemical evidence of progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
