Autor: |
Michal Mego, Barbora Vlkova, Gabriel Minarik, Zuzana Cierna, Marian Karaba, Juraj Benca, Tatiana Sedlackova, Dana Cholujova, Paulina Gronesova, Katarina Kalavska, Daniel Pindak, Jozef Mardiak, Peter Celec |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Frontiers in Oncology, Vol 12 (2022) |
Druh dokumentu: |
article |
ISSN: |
2234-943X |
DOI: |
10.3389/fonc.2022.950451 |
Popis: |
BackgroundCirculating tumor cells (CTCs) contribute to the metastatic cascade and represent an independent survival predictor in breast cancer (BC) patients. Vitamin D has pleiotropic effects, and its low concentrations are associated with breast cancer and metastasis. The aim of this study was to assess plasma vitamin D in primary BC patients in relation to CTCs.MethodsThis study included 91 non-metastatic BC patients (stage I–III) and 24 healthy donors. Blood samples for the analyses were drawn at the time of surgery. CTCs were assessed using a quantitative RT-PCR assay for expression of epithelial (CK19) or epithelial-to-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, and ZEB1). Total 25-OH vitamin D was measured in plasma using ELISA. Plasma cytokines and angiogenic factors were measured by enzyme-linked immunoassay.ResultsCTCs were detected in 30 (33%) patients. Patients with detectable CTCs in peripheral blood had significantly lower vitamin D concentrations in comparison to patients without detectable CTCs ((mean ± SD) 8.50 ± 3.89 µg/L for CTC-positive vs 9.69 ± 3.49 µg/L for CTC-negative patients, p = 0.03). The mean ( ± SD) vitamin D plasma level was 9.3 ± 3.65 µg/L for breast cancer patients compared to 18.6 ± 6.8 for healthy donors (p < 0.000001). There was no association between plasma vitamin D and other patient/tumor characteristics. Plasma vitamin D levels are inversely correlated with plasma TGF-β1, TGF-β2, IL β, IL-5, and eotaxin (all p < 0.05). Patients with vitamin D above the median had a better overall survival (hazard ratio (HR) = 0.36, 95% CI 0.16–0.80, p = 0.017), and combined analysis showed the best survival for CTC-negative patients with vitamin D levels above the median as compared to patients with opposite characteristics (HR = 0.18, 95% CI 0.05–0.63, p = 0.004).ConclusionsLow vitamin D could be a consequence and hence a biomarker of a more invasive disease. Alternatively, vitamin D could be associated with survival because of its role in tumor dissemination. Whether its supplementation affects the metastatic cascade should be tested in animal experiments and interventional studies. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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