Fig. 6. DNA methylome and transcriptome profiling of TP53/CDKN2A^KO GEJ organoids.

(A) A volcano plot showing differentially expressed genes (DEGs) in TP53/CDKN2A^KO organoids versus control organoids. Data represent four biological replicates. (B) Gene ontology (GO) analysis identified top ranked key terms of biological processes and cellular components enriched in DEGs in TP53/CDKN2A^KO versus control organoids. (C) A volcano plot showing differentially methylated CpGs (red hypermethylated in control and blue hypermethylated in TP53/CDKN2A^KO) and (D) column plots showing DMRs in TP53/CDKN2A^KO versus control organoids. (E) Top ranked transcription factor (TF) binding motifs from the forkhead box (FOX) family enriched in hypomethylated differentially methylated regions (DMRs) in TP53/CDKN2A^KO versus control organoids. P values were calculated using the HOMER package. P1, patient 1; P2, patient 2; P3, patient 3. (F) Dot plots showing expression of FOX family TFs in TP53/CDKN2A^KO versus control organoids (bottom dots, n = 4 biological replicates) and in EAC tumors (n = 88) versus normal GEJ samples (n = 9) from the TCGA (top dots). Genes are ranked on the basis of the −log10 (P value) comparing EAC tumors with normal GEJ samples. The dot size denotes −log10 (P value); color indicates log₂ fold change; missing dots correspond to undetectable mRNA expressions.