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Plasma oxysterol levels in luminal subtype breast cancer patients are associated with clinical data.

ABSTRACT: 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, 7?-hydroxycholesterol, 7-ketocholesterol, cholesterol-5?,6?-epoxide, cholesterol-5?,6?-epoxide, and cholestane-3?,5?,6?-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-5?,6?-epoxide were detected in patient plasma samples. Circulating levels of 7?-hydroxycholesterol and 27-hydroxycholesterol were significantly lower in patients with small tumors (pT1) and cholesterol-5?,6?-epoxide and cholestane-3?,5?,6?-triol were lower in patients with stage IA disease compared to larger tumors or more advanced stages. Patients with higher than median cholestane-3?,5?,6?-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-3?,5?,6?-triol, may have prognostic roles in patients with luminal subtype breast cancer.

SUBMITTER: Kloudova-Spalenkova A

PROVIDER: S-EPMC7015808 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Plasma oxysterol levels in luminal subtype breast cancer patients are associated with clinical data.

Kloudova-Spalenkova Alzbeta A Ueng Yune-Fang YF Wei Shouzou S Kopeckova Katerina K Peter Guengerich F F Soucek Pavel P

The Journal of steroid biochemistry and molecular biology 20191223

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, 7 ...[more]

PMID: 31874216

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Project description:ImportanceIn bacterial sepsis, CD14 and its N-terminal fragment (soluble CD14 subtype, "Presepsin") have been characterized as markers of innate immune responses and emerging evidence has linked both to coronavirus disease 2019 pathophysiology.ObjectivesOur aim was to determine the relationship between the soluble form of CD14 and soluble CD14 subtype plasma levels, coronavirus disease 2019 status, and coronavirus disease 2019-related outcomes.DesignA prospective cohort study.SettingICUs in three tertiary hospitals in Seattle, WA.ParticipantsTwo-hundred four critically ill patients under investigation for coronavirus disease 2019.Main outcomes and measuresWe measured plasma soluble CD14 and soluble CD14 subtype levels in samples collected upon admission. We tested for associations between biomarker levels and coronavirus disease 2019 status. We stratified by coronavirus disease 2019 status and tested for associations between biomarker levels and outcomes.ResultsAmong 204 patients, 102 patients had coronavirus disease 2019 and 102 patients did not. In both groups, the most common ICU admission diagnosis was respiratory failure or pneumonia and proportions receiving respiratory support at admission were similar. In regression analyses adjusting for age, sex, race/ethnicity, steroid therapy, comorbidities, and severity of illness, soluble CD14 subtype was 54% lower in coronavirus disease 2019 than noncoronavirus disease 2019 patients (fold difference, 0.46; 95% CI, 0.28-0.77; p = 0.003). In contrast to soluble CD14 subtype, soluble CD14 levels did not differ between coronavirus disease 2019 and noncoronavirus disease 2019 patients. In both coronavirus disease 2019 and noncoronavirus disease 2019, in analyses adjusting for age, sex, race/ethnicity, steroid therapy, and comorbidities, higher soluble CD14 subtype levels were associated with death (coronavirus disease 2019: adjusted relative risk, 1.21; 95% CI, 1.06-1.39; p = 0.006 and noncoronavirus disease 2019: adjusted relative risk, 1.19; 95% CI, 1.03-1.38; p = 0.017), shock, and fewer ventilator-free days. In coronavirus disease 2019 only, an increase in soluble CD14 subtype was associated with severe acute kidney injury (adjusted relative risk, 1.23; 95% CI, 1.05-1.44; p = 0.013).ConclusionsHigher plasma soluble CD14 subtype is associated with worse clinical outcomes in critically ill patients irrespective of coronavirus disease 2019 status though soluble CD14 subtype levels were lower in coronavirus disease 2019 patients than noncoronavirus disease 2019 patients. Soluble CD14 subtype levels may have prognostic utility in coronavirus disease 2019.

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Plasma oxysterol levels in luminal subtype breast cancer patients are associated with clinical data.

Publications

Plasma oxysterol levels in luminal subtype breast cancer patients are associated with clinical data.

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