Fig. 4: Functional consequences of 9p21 gene LoF in BE and EAC.
a, Frequency of damaged 9p21 genes in the four groups estimated over n = 22 patients with NP-BE, n = 108 patients with P-BE and n = 337 patients with EAC with matched genomic and transcriptomic data. b, Proportions of samples with LoF in KLHL9 (N), IFNE (T), MTAP (U), and CDKN2B (W) and DMRTA1 (X) over samples with CDKN2A LoF (V) in each group of NP-BEs, P-BEs and EACs. The number of samples in each group and condition is reported. c, Relative proportion of dysregulated pathways in NP-BE, P-BE and EAC cohorts mapping to cell cycle regulation, metabolism, signal transduction, immune response and development. Numbers in brackets represent the number of unique pathways. d–f, Results of pre-ranked GSEA48 showing the normalized enrichment score (NES), FDR and gene ratio (number of leading-edge genes over the total expressed genes) of pathways dysregulated in each group of NP-BEs (d), P-BEs (e) and EACs (f). NES > 0 indicates pathway upregulation, whereas NES < 0 indicates downregulation. P values were estimated by permutation and corrected for multiple testing using the Benjamini–Hochberg method. g,h, Fold change of expression and correlation plot of the shared leading-edge (LE) genes of interferon gamma (g) and alpha (h) response pathways enriched in P-BE and EAC group 2 as compared to 9p21 wild-type samples. Coefficients and associated P values from two-sided Pearson’s correlation test are reported for both pathways. i, Overlap of leading-edge genes between interferon gamma and alpha response pathways enriched in P-BE and EAC group 2. The 19 shared genes are listed. FC, fold change.
