Expression of oxysterol pathway genes in oestrogen-positive breast carcinomas.
OBJECTIVE
This study investigated whether gene expression levels of key modulators of the oxysterol signalling pathway modify the prognosis of patients with oestrogen receptor-positive (ER+) breast carcinomas via interaction with endocrine therapy.


BACKGROUND
The prognosis of patients with ER+ breast carcinoma depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to oestrogen receptor and anti-oestrogen binding site which may deregulate cholesterol homoeostasis and influence effect of therapy.


METHODS
The expression levels of 70 oxysterol pathway genes were evaluated in a test set of breast carcinomas differing in ER expression. The genes differentially expressed in ER+ tumours were assessed in a comprehensive set of ER+ tumours to evaluate their clinical significance.


METHODS
A total of 193 primary patients with breast carcinoma were included.


METHODS
The transcript levels were determined by quantitative real-time polymerase chain reaction.


RESULTS
The expression levels of 23 genes were found to be specifically dysregulated in ER+ tumours compared to ER- tumours of the test set. The expression levels of ABCG2, CYP7B1, CYP24A1, CYP39A1 and CH25H genes were found to be strongly associated with disease stage; however, none of the gene expression levels were associated with disease-free survival in patients treated with endocrine therapy.


CONCLUSIONS
The expression of a number of oxysterol pathway genes is significantly modulated by ER expression and associated with the clinical stage of patients. However, the expression of oxysterol pathway genes was not found to modify the prognosis of ER+ patients with breast carcinoma treated with endocrine therapy.
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.|Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Alzbeta
A
Kloudova
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Veronika
V
Brynychova
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Radka
R
Vaclavikova
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.|Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
David
D
Vrana
Department of Surgery, Hospital Atlas, Zlin, Czech Republic.|University of Tomas Bata in Zlin, Zlin, Czech Republic.
Jiri
J
Gatek
Department of Pathology & Molecular Medicine, Second Faculty of Medicine, Charles University & Motol University Hospital, Prague, Czech Republic.
Marcela
M
Mrhalova
Department of Pathology & Molecular Medicine, Second Faculty of Medicine, Charles University & Motol University Hospital, Prague, Czech Republic.
Roman
R
Kodet
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.|Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Pavel
http://orcid.org/0000-0002-4294-6799
P
Soucek
D000368:Aged; D053898:Biosynthetic Pathways / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000494:pharmacology; D018572:Disease-Free Survival; D004703:Endocrine System; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D000072376:Oxysterols / Q000378:metabolism*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis
D000072376:Oxysterols; D011960:Receptors, Estrogen; D002784:Cholesterol
breast carcinoma; expression; oestrogen receptor; oxysterols; prognosis