Fig. 3: Super-enhancer signatures in primary and lymph node tumors.

a Percentage of predicted typical enhancers and super-enhancers (SE) across Nor (n = 10), EC (n = 10), and LNC (n = 8) tissues showing H3K27ac enrichment above that of randomly selected regions (99%) across an increasing number of patients. b Gene Ontology (GO) analysis of the top 2000 predicted typical enhancer-linked genes and SE-associated genes; the top significantly associated biological processes are presented. c–e A total of 1317 super-enhancers are ranked by their differential H3K27ac intensity between EC and Nor, LNC and Nor, as well as LNC and EC samples. Genes associated with the top gained and lost SEs are listed; oncogenes are highlighted in red, and tumor suppressors are highlighted in blue. f, g Fold changes in H3K27ac enrichment signals (f) and expression levels for differential SE-associated genes (g) (EC/Nor, LNC/Nor, or LNC/EC) and for differential SE (gained and lost)-associated genes (EC vs. Nor, LNC vs. Nor, or LNC vs. EC). Unaltered SE-associated genes were used as controls. Data points represent means of Nor (n = 10), EC (n = 10), and LNC (n = 8) samples. Boxes correspond to interquartile ranges (IQR), thick black lines indicate the median values, and the whiskers extend to the lowest or highest data point that are still within 1.5 IQR of the bottom or top quartile, respectively. P value was calculated by the two-sided Wilcoxon test (no adjustments). *P < 10e-10, **P < 10e-20, ***P < 10e-30. h Cancer hallmark analysis using differentially predicted SEs showing recurrently gained, recurrently lost, and unaltered H3K27ac signals in EC or LNC relative to Nor. The log (adjust P value) obtained from the hypergeometric test is shown. i, j Survival analysis comparing groups of patients with high or low expression of the top common lost (i) or gained (j) SE-associated genes in ESCC TCGA data using Kaplan–Meier plotter. A poor prognosis observed for ESCC patients with tumors possessing a high expression signature of gained SE-associated genes and a low expression signature of lost SE-associated genes. Survival data are presented every 20 months. A Log-rank test was performed for survival data. Source data are provided as a Source Data file.