ABCA transporter gene expression and poor outcome in epithelial ovarian cancer

Hedditch, Ellen L., Gao, Bo, Russell, Amanda J., Lu, Yi, Emmanuel, Catherine, Beesley, Jonathan, Johnatty, Sharon E., Chen, Xiaoqing, Harnett, Paul, George, Joshy, Williams, Rebekka T., Flemming, Claudia, Lambrechts, Diether, Despierre, Evelyn, Lambrechts, Sandrina, Vergote, Ignace, Karlan, Beth, Lester, Jenny, Orsulic, Sandra, Walsh, Christine, Fasching, Peter, Beckmann, Matthias W., Ekici, Arif B., Hein, Alexander, Matsuo, Keitaro, Hosono, Satoyo, Nakanishi, Toru, Yatabe, Yasushi, Pejovic, Tanja, Bean, Yukie, Heitz, Florian, Harter, Philipp, du Bois, Andreas, Schwaab, Ira, Hogdall, Estrid, Kjaer, Susan K., Jensen, Allan, Hogdall, Claus, Lundvall, Lene, Engelholm, Svend Aage, Brown, Bob, Flanagan, James, Metcalf, Michelle D., Siddiqui, Nadeem, Sellers, Thomas, Fridley, Brooke, Cunningham, Julie, Schildkraut, Joellen, Iversen, Ed, Weber, Rachel P., Berchuck, Andrew, Goode, Ellen, Bowtell, David D., Chenevix-Trench, Georgia, deFazio, Anna, Norris, Murray D., MacGregor, Stuart, Haber, Michelle and Henderson, Michelle J. (2014) ABCA transporter gene expression and poor outcome in epithelial ovarian cancer. Journal of the National Cancer Institute, 106 7: 1-11. doi:10.1093/jnci/dju149

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Author Hedditch, Ellen L.
Gao, Bo
Russell, Amanda J.
Lu, Yi
Emmanuel, Catherine
Beesley, Jonathan
Johnatty, Sharon E.
Chen, Xiaoqing
Harnett, Paul
George, Joshy
Williams, Rebekka T.
Flemming, Claudia
Lambrechts, Diether
Despierre, Evelyn
Lambrechts, Sandrina
Vergote, Ignace
Karlan, Beth
Lester, Jenny
Orsulic, Sandra
Walsh, Christine
Fasching, Peter
Beckmann, Matthias W.
Ekici, Arif B.
Hein, Alexander
Matsuo, Keitaro
Hosono, Satoyo
Nakanishi, Toru
Yatabe, Yasushi
Pejovic, Tanja
Bean, Yukie
Heitz, Florian
Harter, Philipp
du Bois, Andreas
Schwaab, Ira
Hogdall, Estrid
Kjaer, Susan K.
Jensen, Allan
Hogdall, Claus
Lundvall, Lene
Engelholm, Svend Aage
Brown, Bob
Flanagan, James
Metcalf, Michelle D.
Siddiqui, Nadeem
Sellers, Thomas
Fridley, Brooke
Cunningham, Julie
Schildkraut, Joellen
Iversen, Ed
Weber, Rachel P.
Berchuck, Andrew
Goode, Ellen
Bowtell, David D.
Chenevix-Trench, Georgia
deFazio, Anna
Norris, Murray D.
MacGregor, Stuart
Haber, Michelle
Henderson, Michelle J.
Title ABCA transporter gene expression and poor outcome in epithelial ovarian cancer
Journal name Journal of the National Cancer Institute   Check publisher's open access policy
ISSN 1460-2105
Publication date 2014-07-09
Year available 2014
Sub-type Article (original research)
DOI 10.1093/jnci/dju149
Open Access Status Not yet assessed
Volume 106
Issue 7
Start page 1
End page 11
Total pages 11
Place of publication Oxford, England, U.K.
Publisher Oxford University Press
Language eng
Subject 1306 Cancer Research
2730 Oncology
Abstract Background 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 of high-grade serous EOC tumors was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. Associations between clinical outcomes and ABCA transporter gene single nucleotide polymorphisms were tested in a genome-wide association study. 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. All statistical tests were two-sided. Results Associations with outcome were observed with ABC transporters of the A subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009 were associated with shorter overall survival (hazard ratio for death = 1.50; 95% confidence interval [CI] =1.26 to 1.79; P = 6.5e-6). The combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with particularly poor outcome (mean overall survival in group with adverse ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P =. 001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. Conclusions Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC.
Keyword Oncology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DAMD17-01-1-0729
RO1 CA 61107
94 222 52
R01 CA122443
P50 CA136393
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 26 Mar 2015, 19:57:34 EST by Matthew Lamb on behalf of School of Medicine