Fig. 5

cfDNA Methylation profiles in HCC patients match our in vitro findings. a Study set-up. For each patient, a sample at treatment onset was collected. For the three intrinsically resistant patients, a second sample was taken at first follow-up, corresponding to the end of treatment. For the six patients with acquired resistance, a second sample was taken under treatment, while still responsive, and a third upon resistance acquisition, corresponding to the end of treatment. For the three patients showing durable response, a second sample was collected at the end of the study. b Boxplots depict methylation levels of target CpGs in samples from 16 control subjects (blue) and 12 HCC patients (yellow). Samples are ordered according to mean target CpG methylation. c Correlation between the target CpG methylation levels in HCC patients (TCGA, n = 370; mean depicted on the x-axis) and corresponding levels in first (black) and last (red) liquid biopsies of Patient 1 (y-axis). Correlation direction coefficients depicted by the straight lines indicate cfDNA fractions estimated to originate from tumor tissue. See ‘Methods’ for details. d Bar plots depict the estimated fraction ctDNA in each sample for HCC patients (left panel, start samples in black and follow-up samples in red) and control samples (right panel, blue). e Evolution in time (days under treatment; x-axis) of estimated methylation levels of epithelial (gray) and mesenchymal (red) gene promoter CpGs (y-axis). Shown are means ± SEM. Panels in left half show data for acquired resistance patients, on the upper right for responding patients, and on the lower right for intrinsically resistant patients. f Evolution in time (days under treatment; x-axis) of mean epithelial minus mean mesenchymal gene promoter methylation (y-axis), relative to the t₀ (time point 0) situation. Shown are data from patients with acquired resistant (red), responding patients (blue), and intrinsically resistant patients (green)