Abstract 330A: Differential expression of angiogenic genes in invasive high grade serous ovarian carcinomas.

Abstract

Abstract Our objective is to establish quantifiable and reproducible biomarkers that can aid in prognosis, and predicting treatment outcome in invasive high-grade serous ovarian cancer (HGSC). The goal of this project is to identify genomic determinants that affect the tumor angiogenesis as defined by microvascular density (MVD) count. Our central hypothesis is: differences in angiogenic gene expression profiles are associated with variations in MVD. This is a retrospective pilot study. Under an approved IRB protocol, between 1988 and 2001, sixty five snap frozen invasive serous ovarian cancer tissue samples were gathered at Duke University Medical Center. RNA from those samples were extracted and analyzed by the Affymetrix U133A microarray. Fifty-one of those samples belonged to patients with HGSC. MVD counts were determined for those samples using CD31 and CD105. CD31 and 105 are markers of proliferating endothelial cells and neoangiogenesis. Approximately 285 probe sets (associated with 148 genes) involved in angiogenesis and vasculogenesis were screened. Association between the gene expression levels and MVD counts based on a continuous variable and overall survival of the patients were evaluated. Our results indicate that: i) median CD105-MVD and CD31-MVD counts were 30 and 33, respectively; ii) there was a marginal association between CD105-MVD and overall survival (p-value =0.045) and CD31-MVD and overall survival (OS) (p-value =0.028); iii) CUL7, a member of CULLIN family of ubiquitin ligases, is associated with overall survival of the HGSC patients. Higher expression levels of CUL7 is related to worsening of OS (p-value= 8.17E−05); iv) a stronger association between CD105-MVD count and CUL7 expression (p-value= 0.001), compared to the association between CD31-MVD count and CUL7 expression (p-value= 0.024). In conclusion: CUL 7 has previously been implicated as an antiapoptotic oncogene and a P53 suppressor. Mutations in CUL7 have been linked to abnormal vasculogenesis. CUL2, another member of CULLIN family of ubiquitin ligases has also been implicated in the activity of Hypoxia-Inducible Factor (HIFα) and vasculogenesis. In this study we report that higher expression of CUL7 is significantly associated with worsening of the OS of patients with HGSC. These are considered preliminary results which need to be further verified and validated in an independent data set in future studies. Citation Format: Sharareh Siamakpour- Reihani, Chen Jiang, Taylor Turner, Kouros Owzar, Andrew Berchuck, Mark Dewhirst, Angeles Alvarez Secord. Differential expression of angiogenic genes in invasive high grade serous ovarian carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 330A. doi:10.1158/1538-7445.AM2013-330A