Related Experiment Video
Updated: Apr 27, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
ABCA transporter gene expression and poor outcome in epithelial ovarian cancer
Ellen L Hedditch1, Bo Gao1, Amanda J Russell1
1Affiliations of authors: Children's Cancer Institute Australia, Randwick, Australia (ELH, AJR, RTW, CF, MDN, MH, MJH); Department of Gynaecological Oncology and Westmead Institute for Cancer Research (BG, CE, AOCSG, AdF), Crown Princess Mary Cancer Centre and Westmead Institute for Cancer Research (PH) University of Sydney at the Westmead Millennium Institute, Westmead Hospital, Sydney, Australia; Queensland Institute of Medical Research, Brisbane, Australia (YL, JB, SEJ, XC, AOCSG, GC-T, SM); Peter MacCallum Cancer Centre, Melbourne, Australia (JG, AOCSG, DDB); Vesalius Research Center, VIB, Leuven, Belgium (DL); Department of Oncology, University of Leuven and University Hospitals Leuven, Leuven, Belgium (ED, SL, IV); Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BK, JL, SO, CW); Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg, Erlangen, Germany (PF, MWB, AH); University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA (PF); Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan (ABE, KM, SH); Department of Gynecology (TN), and Department of Pathology and Molecular Diagnostics (YY), Aichi Cancer Center Central Hospital, Nagoya, Aichi, Japan; Department of Obstetrics and Gynecology (TP, YB), and Knight Cancer Institute (TP, YB), Oregon Health & Science University, Portland, OR; Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Erlangen, Germany (FH); Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/ Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany (FH); De
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.
Related Concept Videos
01:31ABC Transporters: Exporter
01:16Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
01:27ABC Transporters: Importer
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
01:06Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...