Figure 5. Validation of retroelement (RE) methylation subtypes in the CPTAC ccRCC cohort.

A NEMO-based clustering (k=3) of REMP-predicted Alu, LINE-1 (L1), and LTR methylation in the CPTAC cohort identifies three RE-defined subtypes (Repressed, Transient, Active) with coordinated global methylation patterns consistent with those observed in TCGA. B Kaplan–Meier overall survival analysis shows separation of RE subtypes, with the Repressed group exhibiting the most favorable outcomes. Overall log-rank test significant (p = 0.16) and multivariable Cox regression adjusting for clinical covariates (HR_adj = 4.7, 95% CI: 1.2–18.8; p = 0.025) are shown. C–H Violin and box plots show molecular and immune features across RE subtypes, including EPAS1 (HIF2A) mRNA expression, PDCD1 (PD-1) mRNA expression, CD8⁺ T cell proportions, progenitor exhaustion scores, and terminal exhaustion scores. Box plots indicate median and interquartile range; violins show distribution density. Pairwise comparisons were performed using Wilcoxon rank-sum tests with multiple-testing adjustment, with adjusted p values shown.