Abstract 1660: Cholesterol efflux transporter gene expression predicts clinical outcome in serous ovarian cancer

Ovarian cancer is a devastating disease. More than half the women diagnosed with advanced disease will die within five years. Tumours displaying serous histology are the most common, and although initially responsive to current chemotherapy regimens, the disease is characterised by a frequent rate of relapse, often with disease that is resistant to further treatment. Tumours displaying serous histology are the most common and often have the worst prognosis. The ATP-binding cassette (ABC) transporter superfamily consists of 48 functional transmembrane proteins which are further classified into seven subfamilies according to sequence similarity, designated A through G. Various members of the B, C and G branches are well-known for their abilities to convey drug resistance to cancer cells in vitro, but their precise roles in determining clinical outcome are still unclear. In addition, ABC transporters have important and diverse physiological roles through active transport of a variety of endogenous substrates, which could also contribute to tumour phenotype and treatment response. This is the first study to explore the entire ABC transporter gene family in relation to clinical outcome of ovarian cancer. Using a Taqman low density array format for real-time PCR, we examined expression of all ABC transporter genes in a cohort of 150 serous ovarian cancers. Kaplan-Meier survival analysis revealed that expression of multiple ABCA family transporters was significantly associated with progression-free or overall survival and multivariate modelling identified ABCA1, ABCA5, ABCA6, ABCA8 and ABCA9 as new prognostic markers for serous ovarian cancer that are independent of established clinical indicators. The prognostic significance of ABCA family transporter expression was validated in an independent microarray dataset consisting of 350 serous tumours available through The Cancer Genome Atlas. These ABCA family transporters are not known to transport drugs but instead function in cellular lipid trafficking and cholesterol homeostasis, suggesting that treatment failure may involve mechanisms other than simple efflux of chemotherapeutic drugs. In light of accumulating evidence for the importance of cholesterol and bioactive lipids in several cancers, this study highlights an important area for investigation into the biology and treatment of serous ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1660. doi:10.1158/1538-7445.AM2011-1660