Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients

Abstract Programmed death ligand 1 (PD-L1) overexpression has been associated with poor clinical outcomes in several human cancers whose increased malignant behaviour might be related to PD-L1 mediated systemic immunological tolerance. This study aims to verify if circulating cytokines may serve as...

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Autores principales: Zuzana Cierna, Bozena Smolkova, Dana Cholujova, Paulina Gronesova, Svetlana Miklikova, Marina Cihova, Jana Plava, Michal Mego
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:0c8a61ac91ed49e2ab85bcac9794a1e92021-12-02T14:01:24ZDecreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients10.1038/s41598-020-80351-92045-2322https://doaj.org/article/0c8a61ac91ed49e2ab85bcac9794a1e92021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80351-9https://doaj.org/toc/2045-2322Abstract Programmed death ligand 1 (PD-L1) overexpression has been associated with poor clinical outcomes in several human cancers whose increased malignant behaviour might be related to PD-L1 mediated systemic immunological tolerance. This study aims to verify if circulating cytokines may serve as a proxy for non-invasive identification of sensitive prognostic biomarkers reflecting tumour and its microenvironment. Immunohistochemistry was used to measure PD-L1 expression in tumour tissue sections of 148 chemonaïve breast cancer (BC) patients. The panel of 51 cytokines was analysed using multiplex bead arrays. High PD-L1 expression in tumours was associated with shorter progression-free survival (HR 3.25; 95% CI 1.39–7.61; P = 0.006) and low circulating levels of three multifunctional molecules; VEGF, TNF-β and IL-15 (P = 0.001). In multivariate analysis, patients with low VEGF had 4.6-fold increased risk of PD-L1 overexpression (P = 0.008), present in 76.5% of patients with all these three cytokines below the median (vs. 35.6% among the others; P = 0.002). The area under the curve value of 0.722 (95% CI 0.59–0.85; P = 0.004) shows that this combination of cytokines has a moderate ability to discriminate between PD-L1 high vs. PD-L1 low patients. Plasma cytokines, therefore, could serve as potential non-invasive biomarkers for the identification of high-risk BC cases.Zuzana CiernaBozena SmolkovaDana CholujovaPaulina GronesovaSvetlana MiklikovaMarina CihovaJana PlavaMichal MegoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Zuzana Cierna
Bozena Smolkova
Dana Cholujova
Paulina Gronesova
Svetlana Miklikova
Marina Cihova
Jana Plava
Michal Mego
Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients
description Abstract Programmed death ligand 1 (PD-L1) overexpression has been associated with poor clinical outcomes in several human cancers whose increased malignant behaviour might be related to PD-L1 mediated systemic immunological tolerance. This study aims to verify if circulating cytokines may serve as a proxy for non-invasive identification of sensitive prognostic biomarkers reflecting tumour and its microenvironment. Immunohistochemistry was used to measure PD-L1 expression in tumour tissue sections of 148 chemonaïve breast cancer (BC) patients. The panel of 51 cytokines was analysed using multiplex bead arrays. High PD-L1 expression in tumours was associated with shorter progression-free survival (HR 3.25; 95% CI 1.39–7.61; P = 0.006) and low circulating levels of three multifunctional molecules; VEGF, TNF-β and IL-15 (P = 0.001). In multivariate analysis, patients with low VEGF had 4.6-fold increased risk of PD-L1 overexpression (P = 0.008), present in 76.5% of patients with all these three cytokines below the median (vs. 35.6% among the others; P = 0.002). The area under the curve value of 0.722 (95% CI 0.59–0.85; P = 0.004) shows that this combination of cytokines has a moderate ability to discriminate between PD-L1 high vs. PD-L1 low patients. Plasma cytokines, therefore, could serve as potential non-invasive biomarkers for the identification of high-risk BC cases.
format article
author Zuzana Cierna
Bozena Smolkova
Dana Cholujova
Paulina Gronesova
Svetlana Miklikova
Marina Cihova
Jana Plava
Michal Mego
author_facet Zuzana Cierna
Bozena Smolkova
Dana Cholujova
Paulina Gronesova
Svetlana Miklikova
Marina Cihova
Jana Plava
Michal Mego
author_sort Zuzana Cierna
title Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients
title_short Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients
title_full Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients
title_fullStr Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients
title_full_unstemmed Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients
title_sort decreased levels of circulating cytokines vegf, tnf-β and il-15 indicate pd-l1 overexpression in tumours of primary breast cancer patients
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0c8a61ac91ed49e2ab85bcac9794a1e9
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