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

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Please use this identifier to cite or link to this item: http://140.128.103.80:8080/handle/310901/28839

Title:	Hypermethylation of the TGF-beta target, ABCA1 is associated with poor prognosis in ovarian cancer patients
Authors:	趙偉廷 Chou, Jian-Liang Huang, Rui-Lan Shay, Jacqueline Chen, Lin-Yu Lin, Sheng-Jie Yan, Pearlly S Chao, Wei-Ting Lai, Yi-Hui Lai, Yen-Ling Chao, Tai-Kuang Lee, Cheng-I Tai, Chien-Kuo Wu, Shu-Fen Nephew, Kenneth P Huang, Tim H-M Lai, Hung-Cheng
Contributors:	Department of Life Science, National Chung Cheng University Department of Obstetrics and Gynecology, Shuang Ho Hospital Ohio State University Department of Life Science, Tunghai University Department of Pathology, Tri-Service General Hospital Department of Cellular and Integrative Physiology, Indiana University School of Medicine University of Texas Health Science Center Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University
Keywords:	Ovarian cancer Epigenetics ABCA1
Date:	2015-01
Issue Date:	2016-11-10T01:29:39Z (UTC)
Publisher:	BioMed Central
Abstract:	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.
Relation:	Clinical Epigenetics, 7, 1
Appears in Collections:	[生命科學系所] 期刊論文

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