Aim: Epithelial Ovarian Cancer (EOC) is a devastating disease with a poor survival rate. Eighty percent of patients relapse within 5 years, often with drug resistant disease. Serous EOC is the most common type and has the poorest survival rate. A better understanding of the contributing factors will help to optimize chemotherapy drug selection and improve treatment outcome for individual patients. ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown.
Methods: The relationship between clinical outcomes and ABC transporter gene expression in two independent cohorts (n=147, n=407) of high-grade serous EOC tumours was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. The impact of short interfering RNA–mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan–Meier analysis and log-rank tests.
Results: High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumours was significantly associated with reduced survival in serous ovarian cancer patients. High ABCA1 mRNA levels were associated with shorter overall survival in the AOCS cohort (n=89) and TCGA cohort (n=407). siRNA mediated suppression of ABCA1 transporter expression was found to impair ovarian cancer cell growth and motility, whilst statin treatment reduced ovarian cell migration.
Discussion: High levels of ABCA transporter expression were associated with poor outcome in serous ovarian cancer. The suppression of cholesterol transporter ABCA1 resulted in reduced growth and motility, therefore implicating it in a more aggressive phenotype in ovarian cancer. Importantly, this study highlights lipid trafficking as a potentially important process in EOC.