Expression of MDR1 in epithelial ovarian cancer and its association with disease progression.
The purposes of this study were to analyze MDR1 expression in ovarian tumors prior to chemotherapy, to correlate the expression with p16, IGFs, ERalpha, and BRCA1, and to examine the association of MDR1 expression with ovarian cancer prognosis. A primary ovarian cancer cohort of 206 patients after surgery was followed up. MDR1, IGFs, ERalpha, p16, and BRCA1 expressions were analyzed in ovarian tumor samples using quantitative real-time PCR. MDR1 was detected in 177 of 206 specimens. MDR1 expression was positively correlated with IGFBP3, ERalpha, p16, and BRCA1, but not correlated with IGF-II, age, and other clinicopathological parameters. MDR1 expression significantly elevated the risk for disease progression (p = 0.02), and this association remained statistically significant after controlling for patient age and clinicopathological parameters or other correlated genes. No association was found between MDR1 expression and overall survival. MDR1 expression may be an independent marker for ovarian cancer progression and combination of different agents targeting different molecules may improve the outcome of ovarian cancer treatment and prevent drug resistance.
Lu
Lingeng
L
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
Katsaros
Dionyssios
D
Wiley
Andrew
A
Rigault de la Longrais
Irene A
IA
Puopolo
Manuela
M
Yu
Herbert
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018450:Disease Progression; D018432:Drug Resistance, Multiple / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047628:Estrogen Receptor alpha; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007335:Insulin-Like Growth Factor II