Fig. 5

Distinctive methylation signatures characterized the EIC of LUSC. A Hierarchical clustering heatmap of 216 CpG methylation values located within 162 immunosuppression-related gene promoters show significant difference between the EIC and the rest class (FDR< 0.05, diff > 0.2). B Boxplot displays the mean methylation levels of 216 CpG sites within 162 immune exhaustion-related gene promoters for 2 classes. Wilcoxon rank-sum test (p<0.0001). Exhausted vs Rest: p=5.1E−15. C–E Correlations between expression and promoter methylation levels for deregulated genes in the EIC to the rest class. CARTN exhibited significantly lower expression in the EIC, while SMAD7, IRF7, CCR4, and MYO1G were synergistically overexpressed (P < 0.001, Wilcoxon rank-sum test). D The expressions of ARTN, SMAD7, IRF7, CCR4, and MYO1G negatively correlated with their promoter methylation level for the whole training cohorts. ESMAD7, IRF7, CCR4, and MYO1G had lower promoter methylation levels mirroring higher expression levels in the EIC, whereas ARTN had an opposite status. Red dots in the plotting represent the members of EIC, and blue dots represent the members of the rest class