Fig. 3: Effect of the LoF of CDKN2A and other 9p21 genes on survival.
a–c, Kaplan–Meier survival curves of n = 1,032 patients with EAC with wild-type CDKN2A compared to those with all types of LoFs (P = 2 × 10−4) (a), only homozygous deletions (P = 6 × 10−3) (b) and only LoF mutations (P = 3 × 10−3) (c). d, Kaplan–Meier survival curves of n = 129 patients with P-BE with and without CDKN2A LoF. Log-rank method was used to estimate the P values. ns, not significant. e, Approach to test the effect of the co-damage in 9p21 genes on patient survival. Only n = 779 patients with EAC with WGS or WES data were used for the survival analysis, whereas n = 337 patients with RNA-seq data were used to measure 9p21 gene expression. Letters correspond to the 26 genes according to their order in the chromosomal locus. f, LoF frequency of 9p21 genes in n = 779 patients with EAC. g, Distribution of normalized expression values in the 9p21 genes in n = 337 patients with EAC. Boxplot shows first and third quartiles, whiskers extend to the lowest and highest value within the 1.5× interquartile range and the line indicates the median. h, Kaplan–Meier survival analysis of patients with EAC with co-alterations in the ten expressed 9p21 genes and n = 413 patients with EAC with a wild-type locus. Only groups with significantly poor survival (FDR < 0.1) are shown and genes of interest are outlined in black. All groups used in the analysis are listed in Supplementary Table 5. The minimum and maximum number and percent of damaged EACs in f and h are reported in the corresponding heatmap. HD, homozygous deletion; WES, whole-exome sequencing; WGS, whole-genome sequencing. Cartoon in (e) was created with BioRender.com.
