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. 2023 Sep 13;14:5669. doi: 10.1038/s41467-023-41434-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Principal component analysis (PCA) depicting the genome-wide mean methylation levels of serum cfDNA derived from patients with meningioma (MNG; n = 63) and non-MNG conditions (other CNS entities and non-neoplastic diseases; n = 141). Note: MNG: meningiomas; CNS Central Nervous System. b Mean methylation levels of the differentially methylated CpG probes (DMP, n = 98) across comparisons between MNG and non-MNG (Wilcoxon rank sum test; Kruskal-Wallis; *p < 0.05, **p < 0.01, ***p < 0.001). Box plots - data are presented as median and upper (75%) and lower (25%) quartiles. Whiskers represent minimum to maximum values, excluding outliers. Exact p-values: Meningioma vs Non-neoplastic Disease: p = 0.018; Meningioma vs Glioma: p = 4.4e−16; Meningioma vs pituitary neuroendocrine tumors: p = 0.017; Glioma vs Other CNS tumors: p = 0.012. Note: DMP: differentially methylated probes. t-distributed stochastic neighbor embedding (t-SNE) plots displaying clustering of meningioma-specific DMPs across MNG and non-MNG tissue specimens (c). A subset of these DMPs is detected in the serum and also distinguish equivalent groups (d). e t-SNE plot displaying dimension-reduced diagnostic-Meningioma Epigenetic Liquid Biopsy (d-MeLB) probes (SMP: n = 18k CpGs) across CNS tumor tissue, liquid biopsy (serum and plasma) and tumor tissue from patients with MNG. SMP similarly methylated probes, LB liquid biopsy. Distribution of the d-MeLB scores across independent cohorts (f: original liquid biopsy serum, n = 93; g: additional MNG serum, n = 19; h: additional MNG plasma, n = 10) (Dashed line: MeLB cutoff score). Box plots - data are presented as median and upper (75%) and lower (25%) quartiles. Whiskers represent minimum to maximum values, excluding outliers. Upper left corner: performance measures. ACC Accuracy, SE Sensitivity, SP Specificity, CUI Clinical Utility Index, MCC Matthew’s Correlation Coefficient, IT initial treated, IU initial untreated, RT recurrent treated, RU recurrence untreated.