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- Title
Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients.
- Authors
Cierna, Zuzana; Smolkova, Bozena; Cholujova, Dana; Gronesova, Paulina; Miklikova, Svetlana; Cihova, Marina; Plava, Jana; Mego, Michal
- 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.
- Subjects
CYTOKINES; PROTEIN expression; BREAST cancer; TUMOR microenvironment; IMMUNOHISTOCHEMISTRY
- Publication
Scientific Reports, 2021, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-80351-9