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

Fig. 2. Serum circulating cell-free DNA methylation patterns and signatures differentiate meningiomas with different behaviors.

Fig. 2

a Methylation heatmap displaying the 1000 most variable methylated probes (β-values) across serum meningioma unsupervised k-clusters (n = 63). Samples are sorted into methylation-based clusters and annotated with clinicopathological/molecular features. Vertical tracks (right) genomic annotations. LI Labeling Index, EOR Extent of Resection, NI non-informed, MRI magnetic resonance imaging b/c. Distribution of the prognostic-Meningioma Epigenetic Liquid Biopsy (p-MeLB) scores across (b) the original independent cohort (n = 23) and (c) additional validations (n = 50) from patients with meningiomas presenting different outcomes (confirmed recurrence or no recurrence; dashed lines: p-MeLB score cutoff). 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. d Scatterplot displaying the relationship between p-MeLB and the nomogram recurrence risk prediction across the primary meningioma tissue subset. Linear relationship is depicted with 95% confidence interval (lower and upper limits). Measurements of concordance are displayed (Cohen’s unweighted kappa/Spearman’s ρ, p < 0.05). Table comparing the accuracies of p-MeLB and the nomogram-based classifier across an independent subset of primary meningioma tissue (n = 69). ACC accuracy, CR Confirmed Recurrence, CNR Confirmed No Recurrence. e Kaplan-Meier survival curves displaying meningioma tumor tissue samples stratified by their predicted recurrence risk (n = 127, vertical ticks: censorship). Survival curves are depicted with 95% confidence intervals (lower and upper limits) for point estimates; comparisons of median survival time in both recurrence risk groups were conducted using log-rank tests (p < 0.0001). MNG meningioma, RR recurrence risk.