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Background  The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family,  ABCA1  was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that  ABCA1  may be involved in ovarian cancer and its initiation.    Results  We first compared the expression level of  ABCA1  in IOSE cells and a panel of ovarian cancer cell lines and found that  ABCA1  was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of  ABCA1  in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of  ABCA1  increased the cholesterol level and promoted cell growth  in vitro  and  in vivo . Further analysis of  ABCA1  methylation in 76 ovarian cancer patient samples demonstrated that patients with higher  ABCA1  methylation are associated with high stage ( P  = 0.0131) and grade ( P  = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of  ABCA1  have shorter overall survival ( P  = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival ( P  = 0.038).    Conclusions   ABCA1  may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients.    Electronic supplementary material  The online version of this article (doi:10.1186/s13148-014-0036-2) contains supplementary material, which is available to authorized users.

Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients