Imperial College London
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DR JAMES M. FLANAGAN

Faculty of Medicine, Department of Surgery & Cancer

Reader in Epigenetics
 
 
 
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Contact

 

+44 (0)20 7594 2127j.flanagan

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hedditch:2014:jnci/dju149,
author = {Hedditch, EL and Gao, B and Russell, AJ and Lu, Y and Emmanuel, C and Beesley, J and Johnatty, SE and Chen, X and Harnett, P and George, J and Williams, RT and Flemming, C and Lambrechts, D and Despierre, E and Lambrechts, S and Vergote, I and Karlan, B and Lester, J and Orsulic, S and Walsh, C and Fasching, P and Beckmann, MW and Ekici, AB and Hein, A and Matsuo, K and Hosono, S and Nakanishi, T and Yatabe, Y and Pejovic, T and Bean, Y and Heitz, F and Harter, P and du, Bois A and Schwaab, I and Hogdall, E and Kjaer, SK and Jensen, A and Hogdall, C and Lundvall, L and Engelholm, SA and Brown, B and Flanagan, J and Metcalf, MD and Siddiqui, N and Sellers, T and Fridley, B and Cunningham, J and Schildkraut, J and Iversen, E and Weber, RP and Berchuck, A and Goode, E and Bowtell, DD and Chenevix-Trench, G and deFazio, A and Norris, MD and MacGregor, S and Haber, M and Henderson, MJ},
doi = {jnci/dju149},
journal = {JNCI: Journal of the National Cancer Institute},
title = {ABCA transporter gene expression and poor outcome in epithelial ovarian cancer},
url = {http://dx.doi.org/10.1093/jnci/dju149},
volume = {106},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundATP-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.MethodsThe 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.ResultsAssociations 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.ConclusionsExpression of ABCA transporters was associate
AU  - Hedditch,EL
AU  - Gao,B
AU  - Russell,AJ
AU  - Lu,Y
AU  - Emmanuel,C
AU  - Beesley,J
AU  - Johnatty,SE
AU  - Chen,X
AU  - Harnett,P
AU  - George,J
AU  - Williams,RT
AU  - Flemming,C
AU  - Lambrechts,D
AU  - Despierre,E
AU  - Lambrechts,S
AU  - Vergote,I
AU  - Karlan,B
AU  - Lester,J
AU  - Orsulic,S
AU  - Walsh,C
AU  - Fasching,P
AU  - Beckmann,MW
AU  - Ekici,AB
AU  - Hein,A
AU  - Matsuo,K
AU  - Hosono,S
AU  - Nakanishi,T
AU  - Yatabe,Y
AU  - Pejovic,T
AU  - Bean,Y
AU  - Heitz,F
AU  - Harter,P
AU  - du,Bois A
AU  - Schwaab,I
AU  - Hogdall,E
AU  - Kjaer,SK
AU  - Jensen,A
AU  - Hogdall,C
AU  - Lundvall,L
AU  - Engelholm,SA
AU  - Brown,B
AU  - Flanagan,J
AU  - Metcalf,MD
AU  - Siddiqui,N
AU  - Sellers,T
AU  - Fridley,B
AU  - Cunningham,J
AU  - Schildkraut,J
AU  - Iversen,E
AU  - Weber,RP
AU  - Berchuck,A
AU  - Goode,E
AU  - Bowtell,DD
AU  - Chenevix-Trench,G
AU  - deFazio,A
AU  - Norris,MD
AU  - MacGregor,S
AU  - Haber,M
AU  - Henderson,MJ
DO  - jnci/dju149
PY  - 2014///
SN  - 0027-8874
TI  - ABCA transporter gene expression and poor outcome in epithelial ovarian cancer
T2  - JNCI: Journal of the National Cancer Institute
UR  - http://dx.doi.org/10.1093/jnci/dju149
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341637400019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/jnci/article/106/7/dju149/1010035
VL  - 106
ER  -
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