Abstract 5081: Dysregulation of soluble EGFr, TIMP-1, EphA2 and CAIX levels in advanced ovarian cancer
Authors: Brown-Shimer Sheryl , Pierce Karen , Newman Dawn , Trivedi Dhaval , Ramirez Jessica , Hamer Peter J. , Bradley Stephen P. , Carney Walter P. 
Published: February 2011

Background: In recent years, survival rates for patients with ovarian cancer have been improving, however, management of patients with advanced ovarian cancer continues to be a difficult clinical problem. Due to tumor heterogeneity, patients often receive expensive therapies with dangerous side-effects to which their tumors do not respond. Soluble biomarkers, particularly when assayed in panels, have the potential to assist clinicians in selecting and monitoring appropriate therapies. Increases in soluble TIMP-1 and CAIX and decreases in soluble EGFR levels have been reported in many cancers, and along with EphA2, are targets for novel cancer therapeutics. To address the utility of using these in a panel for ovarian cancer, we determined serum and plasma levels of all four biomarkers.

Methods: Plasma and sera from stage I -IV ovarian cancer patients were analyzed using the TIMP-1, EGFR, CAIX and EphA2 ELISA assays from Oncogene Science. Levels were then compared to those found in healthy, normal females. Statistical methods used included Kruskal-Wallis test and Dunn's multiple comparison test.

Results: Soluble levels of all four biomarkers were dysregulated in the serum and/or plasma of ovarian cancer patients as compared with levels found in normal healthy, females. For our analysis of serum results, stages I and II were combined and stages III and IV were combined due to the low number of stages I and IV samples in this cohort. Serum levels of TIMP-1 and CAIX were significantly elevated in stages I/II (p = &lt; 0.001 for both markers) and in stages III/IV (p = &lt;0.001 and &lt;0.01, respectively). Serum levels of EGFR were significantly decreased in stages I/II and III/IV (p= &lt; 0.01 and &lt; 0.001, respectively). EphA2 serum levels were not statistically significantly different from normals. In plasma, TIMP-1 levels in stage III (p = &lt;0.001) and stage IV (p = &lt;0.001) were significantly different from normal, but levels in stages I and II were not. CAIX plasma levels were significantly higher in all stages (I, p=&lt;0.05; II, p= &lt;0.001; III, p=&lt;0.001; IV, p=&lt;0.01), and EGFR plasma levels were significantly decreased in stages II (p=&lt;0.05), III (p=&lt;0.001) and IV (p=&lt;0.001), but not in stage I. EphA2 plasma levels were significantly higher than normals in stages I/II (p=&lt;0.05) and stages III/IV (p=&lt;0.001).

Conclusions: EGFR, TIMP-1, CAIX and EphA2 levels in ovarian cancer patients are significantly different from the levels found in normal, healthy females. These markers are dysregulated in early as well as later stages and changes involve both decreases and increases in levels. The fact that these biomarkers behave differently from one another may reflect different biological pathways which could contribute to ovarian tumor heterogeneity. Using these markers as a panel may assist clinicians in selecting the most appropriate therapy for their patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5081.