Fig. 5

A HCC patient subset, which is characterised by an enrichment of genes overexpressed and with hypermethylated CGIs, belongs to the HCC “proliferative-progenitor” subclass. a The 41 HCC patients are classified according to the highest percentage of genes over- versus underexpressed and with hyper- versus hypomethylated CGIs. In orange (left), patients with an enrichment of genes overexpressed and with CGI hypermethylation (H⁺E⁺ patient subset). Patients are organised according to the absolute number of hypermethylated CGIs. The percentage of genes overexpressed and hypermethylated is reported on the top. In green (right), all other patients are reported (NO H⁺E⁺ patient subset). Note that this patient subset is characterised by an enrichment in downregulated genes. Patients are organised according to an enrichment of genes with CGI hypomethylation (top) and hypermethylation (bottom). Concerning the 7 patients of the HCC subgroup 3 identified in Fig. 1f (corresponding to the best overlap patients), 5 of them belong to the H⁺E⁺ subset. Notably, all of these 7 patients are characterised by more than 37% of genes both hypermethylated and overexpressed (highlighted in panel with a red square and a red percentage of genes overexpressed with hypermethylated CGI). The X-axis reports methylation differences, whereas the Y-axis reports expression as Log₂FC. b Transcript levels (from RNA-seq data) of the indicated genes in H⁺E⁺ patient subset (in orange) versus the others (in green). Note significant high transcript levels of AFP, JAG1, NOTCH3, NOTCH4, SOX9, VIM and CD24 in the H⁺E⁺ patient subset. c Transcript levels by RT-qPCR for the same genes shown in b analysed in Alb-R26^Met tumours versus control livers, displaying the same profile of gene upregulation as in the H⁺E⁺ patient subset. Data have been reported in ref.²⁴. Significance is indicated on the top. *P < 0.05, ***P < 0.001