Fig. 5: The proteomic subtypes of diffuse gliomas.
A Consensus-clustering analysis of proteomic profiles identified three proteomic subgroups from the tumor samples: S-Ne (navy, n = 60), S-Pf (yellow, n = 66), and S-Im (red, n = 61). The clinical characteristics, mutational status, and copy number alterations are shown. The heatmap depicted the relative abundance of signature proteins. The pathways that proteins enriched in were labeled on the right. B Kaplan–Meier curves for OS (analyzed samples: n = 187) and PFS (analyzed samples: n = 103) based on proteomic subgroups (log-rank test). C The boxplot indicated the comparisons of the three proteomic subtypes for tumor sizes: S-Ne (green, n = 50), S-Pf (yellow, n = 60), and S-Im (red, n = 53). Two-sided student’s t test. In the box plot, the middle bar represents the median, and the box represents the interquartile range; bars extend to 1.5× the interquartile range. D Kaplan–Meier curves for PFS of patients based on TMZ treatment, in the S-Pf subtype (right, analyzed samples: n = 39), or in the whole cohort (left, analyzed samples: n = 103) (log-rank test). E Kaplan–Meier curves for PFS of EGFRMut&Amp patients, based on TMZ treatment (log-rank test, analyzed samples: n = 9). F Summary of the data and metadata generated in validation cohort. G Kaplan–Meier curves for PFS of based on EGFR mutational status (log-rank test, analyzed samples: n = 34). H, K Scatter plots indicated the correlation between the protein expression and kinase activity of EGFR (H), between the abundance of phosphosite ATRX/T591 and TF activity of ATRX (K), in discovery cohort (left) and in validation cohort (right) (Sample colors: navy: responder; red: non-responder, p: Spearman-rank correlation). I Strategy for screening out phosphor-substrates of EGFR associated with TMZ response. J, L The heatmap showing the global abundance of EGFR and its phosphosubstrates (J), the global abundance of ATRX/T591 and its target genes (L) in discovery (left) and validation cohort (right), Spearman’s correlation between cohorts is shown in the center panel. M Immunohistochemistry of MSH3 and MSH5 (analyzed patients: n = 3), Scale bar = 100 μm. N The systematic diagram summarizing the impact of the mechanism underline both EGFR-mutant and EGFR-amplicon patient were better responded to TMZ treatment. Source data are provided as Source Data files.
