Figure 4

H3K27Me2, H3K27Ac, and H2A1R3Cit histone PTMs present on circulating nucleosome reflects the epigenetic signature of the tumor. (a) Heat map showing the histone PTMs peptides (listed in Supplementary Table 4) differentially abundant between tumor resection tissue (CRC tissues) and normal adjacent tissue (NAT) from the same patients (n = 9 paired samples; p < 0.05). Matched CRC and normal tissues are indicated by the same sample number (from #1 to #9). Data are shown as Log2 ratio of histone PTM levels (log 2 intensity) for a given sample based on average PTM levels across all samples. Log2 Intensity refers to heavy peptide normalized intensity. (b) Volcano plot representing the significance (expressed as -log10(p-value)) as a function of the magnitude of fold change between CRC tissues vs NAT (n = 9 paired samples) of the 79 histone proteoforms identified in plasma. 26 were significantly dysregulated including 4 downregulated (green) and 22 upregulated (red) (p < 0.05). Each plot with a significant fold change is labelled and recorded in Supplementary Table 3. (c) Venn diagram analysis showing the logical relation between the histone PTMs peptides differentially expressed in tumor tissues (blue) and plasma (red), highlighting the 3 common histone PTMs (Other plots are recorded in Supplementary Table 5). (d) Table with log2 intensity value of the 3 common histone PTMs similarly dysregulated in plasma and tumor tissue from the same patient, (n = 9 paired samples; p < 0.05).