Abstract
Background: Soluble PD-L1 (sPD-L1) in the circulation has been documented to activate global immunosuppression and is considered a predictor of negative clinical outcomes in several malignances. However, the clinical significance of sPD-L1 in the peripheral blood and cerebrospinal fluid (CSF) of patients with glioma remains unclear.Objective: The aim of this study was to detect the correlations of sPD-L1 with clinical features in brain tumors and assess the diagnostic value of this protein in gliomas.Methods: Serum samples were obtained from 73 patients with glioma, 20 patients with meningioma, and 49 healthy controls (HCs) in this study. In total, 31 CSF samples were collected from the matched glioma patients, and seven samples were collected from the matched meningioma patients. The expression of serum sPD-L1 in the glioma cohort was followed for 20 days after surgery to examine the kinetics in the circulation. Inflammatory markers were evaluated based on preoperative blood parameters. The sPD-L1 levels in the serum and CSF were determined by enzyme-linked immunosorbent assay (ELISA). The logistic regression model was used to assess the independent associations of sPD-L1 with gliomas, including high-grade gliomas.Results: Serum and CSF levels of sPD-L1 were significantly elevated in patients with gliomas compared to those with meningiomas and HCs. Additionally, increased levels of sPD-L1 were observed in relatively advanced tumors. sPD-L1 overexpression in the CSF appears to be more representative of aggressive tumor features than overexpression in the serum. For glioma diagnosis, both serum and CSF sPD-L1 showed significant value in the diagnosis and stratification of glioma, and the best diagnostic performance was obtained with serum sPD-L1 rather than blood-based inflammatory markers. In addition, a descending trend in the level of serum sPD-L1 was observed in postoperative patients.Conclusion: In gliomas, elevated circulating and CSF sPD-L1 levels are associated with aggressive biological activities. The results of the current study suggest that sPD-L1 is a promising biomarker for gliomas that can be used in clinical practice.
Highlights
Gliomas, which account for the majority of central nervous system (CNS) tumors, are correlated with high rates of recurrence and mortality [1]
The circulatory Soluble programmed death-ligand 1 (PD-L1) (sPD-L1) protein levels exhibited the highest concentrations in the glioma cohort compared with that in the meningioma (0.0688, 0.0454–1.4117; p < 0.001) and healthy control (HC) cohorts (0.1107, 0–0.5908; p < 0.001) (Table 1 and Figure 1A)
The analysis revealed that sPD-L1 (OR: 1.030, p = 0.013) and neutrophil-to-lymphocyte ratio (NLR) (OR: 2.850, p = 0.001) were independent factors for the prediction of high-grade gliomas (HGGs), while the other parameters were not independent predictors (Table S4)
Summary
Gliomas, which account for the majority of central nervous system (CNS) tumors, are correlated with high rates of recurrence and mortality [1] Molecular information such as the mutational status of isocitrate dehydrogenase (IDH) genes and the combined deletion of chromosome arms 1p and 19q (1p/19q codeletion) is integral to the 2016 World Health Organization (WHO) criteria for gliomas [2]. These updates have shifted treatment approaches from histological type-based therapy to genotype-based therapy [3]. The clinical significance of sPD-L1 in the peripheral blood and cerebrospinal fluid (CSF) of patients with glioma remains unclear
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