ABCA Transporter Gene Expression Is Associated With Poor Outcome in Epithelial Ovarian Cancer
In a study reported in the Journal of the National Cancer Institute, Hedditch et al found that expression of ATP-binding cassette (ABC) transporter genes of the A subfamily (ABCA) had a significant impact on outcome in epithelial ovarian cancer.
High ABCA1, Low ABCA5 Expression
Analysis of gene expression in 143 patients with serous epithelial ovarian cancer from a case-control study showed that the only genes with an association of high expression and poor outcome were the ABCA genes ABCA6, ABCA8, and ABCA9, whereas low levels of ABCC11 were associated with poor outcome. In multivariate models adjusting for tumor stage and residual disease after surgery, high expression of ABCA6 was associated with poorer progression-free survival (relative hazard (RH) = 1.61, P = .01) and overall survival (RH = 1.74, P = .02) and high expression of ABCA9 was associated with poorer overall survival (RH = 1.63, P = .03).
Multivariate modeling among patients with ≤ 1 cm residual disease after surgery showed that high expression of the cholesterol transporter gene ABCA1 (RH = 2.10, P = .02, and 1.94, P = .04) and low expression of ABCA5 (RH = 2.04, P = .04, and 2.14, P = .02) together with high expression of ABCA8 (RH = 2.28, P = .01) or ABCA9 (RH = 2.13, P = .01) but not high ABCA6 expression were independently associated with poorer overall survival.
Analysis of single nucleotide polymorphisms showed that low levels of ABCA5 expression and the ABCA5 C-allele rs536009 were associated with shorter overall survival (hazard ratio = 1.50, 95% confidence interval = 1.26–1.79).
Risk Profile
The combined expression pattern of high ABCA1, low ABCA5, and either high ABCA8 or high ABCA9 expression was associated with particularly poor outcome, independent of tumor stage and surgical debulking status. For example, median overall survival in patients with high ABCA1, low ABCA5, and high ABCA9 expression was 33.2 months, compared with 55.3 months in patients with low ABCA1, high ABCA5, and low ABCA9 expression (P = .001).
Associated studies in vitro showed that suppression of the cholesterol transporter ABCA1 resulted in inhibition of ovarian cancer cell growth and migration and that statin treatment reduced cancer cell migration.
The investigators concluded, “Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in [epithelial ovarian cancer].”
Michelle Henderson, PhD, of Children’s Cancer Institute Australia for Medical Research, New South Wales, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by grants from Cancer Australia, Cancer Institute New South Wales, and National Health and Medical Research Council of Australia. The study authors reported no potential conflicts of interest.
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