Abstrakt
Objective: The present study investigated whether gene expression levels of key modulators of the oxysterol signaling pathway modify the prognosis of patients with estrogen receptor positive (ER+) breast carcinomas via interaction with endocrine therapy. Context: The prognosis of ER+ breast carcinoma patients depends on several factors.
Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to estrogen receptor and antiestrogen binding site which may deregulate cholesterol homeostasis and influence effect of therapy. Design: 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+ tumors were assessed in a comprehensive set of ER+ tumors to evaluate their clinical significance. Patients: A total of 193 primary breast carcinoma patients were included.
Measurements: 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+ tumors compared to ER- tumors 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+ breast carcinoma patients treated with endocrine therapy.