Kloudova Alzbeta, Brynychova Veronika, Vaclavikova Radka, Vrana David, Gatek Jiri, Mrhalova Marcela, Kodet Roman, Soucek Pavel
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Clin Endocrinol (Oxf). 2017 Jun;86(6):852-861. doi: 10.1111/cen.13337. Epub 2017 Apr 24.
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.
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.
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.
A total of 193 primary patients with breast carcinoma were included.
The transcript levels were determined by quantitative real-time polymerase chain reaction.
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.
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.
本研究调查了氧甾醇信号通路关键调节因子的基因表达水平是否通过与内分泌治疗的相互作用来改变雌激素受体阳性（ER+）乳腺癌患者的预后。
ER+乳腺癌患者的预后取决于多种因素。先前的研究表明，某些氧化形式的胆固醇（氧甾醇）与雌激素受体和抗雌激素结合位点结合，这可能会破坏胆固醇稳态并影响治疗效果。
在一组ER表达不同的乳腺癌测试集中评估了70个氧甾醇通路基因的表达水平。在一组全面的ER+肿瘤中评估在ER+肿瘤中差异表达的基因，以评估其临床意义。
共纳入193例原发性乳腺癌患者。
通过定量实时聚合酶链反应测定转录水平。
与测试集的ER-肿瘤相比，发现23个基因的表达水平在ER+肿瘤中特异性失调。发现ABCG2、CYP7B1、CYP24A1、CYP39A1和CH25H基因的表达水平与疾病分期密切相关；然而，在接受内分泌治疗的患者中，没有一个基因表达水平与无病生存期相关。
许多氧甾醇通路基因的表达受ER表达的显著调节，并与患者的临床分期相关。然而，未发现氧甾醇通路基因的表达改变接受内分泌治疗的ER+乳腺癌患者的预后。
