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Plasma oxysterol levels in luminal subtype breast cancer patients are associated with clinical data
A. Kloudova-Spalenkova, YF. Ueng, S. Wei, K. Kopeckova, F. Peter Guengerich, P. Soucek,
Language English Country Great Britain
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 GM118122
NIGMS NIH HHS - United States
NV17-28470A
MZ0
CEP Register
- MeSH
- Carcinoma, Ductal, Breast blood pathology MeSH
- Neoplasm Invasiveness MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Biomarkers, Tumor analysis MeSH
- Breast Neoplasms blood pathology MeSH
- Follow-Up Studies MeSH
- Oxysterols blood MeSH
- Prognosis MeSH
- Receptor, ErbB-2 metabolism MeSH
- Receptors, Estrogen metabolism MeSH
- Receptors, Progesterone metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Oxygenated metabolites of cholesterol (oxysterols) have been previously demonstrated to contribute to progression of various cancers and to modulate resistance to breast cancer endocrine therapy in vitro. We measured prognostic roles of circulating levels of seven major oxysterols in the progression of luminal subtype breast carcinoma. Liquid chromatography coupled with tandem mass spectrometry was used for determination of levels of non-esterified 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, 7-ketocholesterol, cholesterol-5α,6α-epoxide, cholesterol-5β,6β-epoxide, and cholestane-3β,5α,6β-triol in plasma samples collected from patients (n = 58) before surgical removal of tumors. Oxysterol levels were then associated with clinical data of patients. All oxysterols except cholesterol-5α,6α-epoxide were detected in patient plasma samples. Circulating levels of 7α-hydroxycholesterol and 27-hydroxycholesterol were significantly lower in patients with small tumors (pT1) and cholesterol-5β,6β-epoxide and cholestane-3β,5α,6β-triol were lower in patients with stage IA disease compared to larger tumors or more advanced stages. Patients with higher than median cholestane-3β,5α,6β-triol levels had significantly worse disease-free survival than patients with lower levels (p = 0.037 for all patients and p = 0.015 for subgroup treated only with tamoxifen). In conclusion, this study shows, for the first time, that circulating levels of oxysterols, especially cholestane-3β,5α,6β-triol, may have prognostic roles in patients with luminal subtype breast cancer.
3rd Faculty of Medicine Charles University Ruska 2411 87 Prague 10 10000 Czech Republic
Institute of Medical Sciences Taipei Medical University Taipei Taiwan ROC
National Research Institute of Chinese Medicine Taipei Taiwan ROC
References provided by Crossref.org
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- $a Kloudova-Spalenkova, Alzbeta $u Department of Toxicogenomics, National Institute of Public Health, Srobarova 48, Prague 10, 10042, Czech Republic; Biomedical Centre, Faculty of Medicine Pilsen, Charles University, alej Svobody 1655/76, Pilsen, 32300, Czech Republic; Third Faculty of Medicine, Charles University, Ruska 2411/87, Prague 10, 10000, Czech Republic.
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- $a Oxygenated metabolites of cholesterol (oxysterols) have been previously demonstrated to contribute to progression of various cancers and to modulate resistance to breast cancer endocrine therapy in vitro. We measured prognostic roles of circulating levels of seven major oxysterols in the progression of luminal subtype breast carcinoma. Liquid chromatography coupled with tandem mass spectrometry was used for determination of levels of non-esterified 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, 7-ketocholesterol, cholesterol-5α,6α-epoxide, cholesterol-5β,6β-epoxide, and cholestane-3β,5α,6β-triol in plasma samples collected from patients (n = 58) before surgical removal of tumors. Oxysterol levels were then associated with clinical data of patients. All oxysterols except cholesterol-5α,6α-epoxide were detected in patient plasma samples. Circulating levels of 7α-hydroxycholesterol and 27-hydroxycholesterol were significantly lower in patients with small tumors (pT1) and cholesterol-5β,6β-epoxide and cholestane-3β,5α,6β-triol were lower in patients with stage IA disease compared to larger tumors or more advanced stages. Patients with higher than median cholestane-3β,5α,6β-triol levels had significantly worse disease-free survival than patients with lower levels (p = 0.037 for all patients and p = 0.015 for subgroup treated only with tamoxifen). In conclusion, this study shows, for the first time, that circulating levels of oxysterols, especially cholestane-3β,5α,6β-triol, may have prognostic roles in patients with luminal subtype breast cancer.
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