Fig. 6: Personalized trajectory reveals six major carcinogenesis tracks of the early ESCCs.

a The trajectory of 746 samples (top) and 114 early ESCC cases were grouped into 9 (bottom). b Sankey diagram analysis of 114 early ESCC cases (top, main cohort) and 49 early ESCC cases (bottom, validation cohort). c Venn diagram showing the track mutations (top) and the CAGs (bottom) (two-sided Fisher’s exact test). CAGs: cancer-associated genes. The overlapped mutations are shown in the box. d The CAG-associated track mutations in the early ESCCs. The co-mutations are highlighted on the left (two-sided Fisher’s exact test), and the mutation frequency is shown on the right. The square directed to a subset of patient samples used for WES (n = 68) in early ESCCs. Co-mutations: *p = 0.032 (TP53 and EPAS1), *p = 0.032 (TP53 and EPHA3), ****p = 9.3E–6 (EPAS1 and EPHA3), *p = 2.2E–7 (STAG2 and USP6), ****p = 9.3E–6 (USP6 and AKAP9), ****p = 3.2E–5 (STAG2 and AKAP9). e GSEA plot (KEGG gene sets) for ECM signaling in EPAS1 mutation and WT comparison. f Venn diagram depicting the number of the overlapped proteins enhanced by the mutation of EPAS1 and T2 enhanced phosphoprotein (top), and the associated biological pathways (bottom). SUPs: the significantly upregulated proteins. g Heatmap showing the represented protein in the cell–cell adhesion positive associated with EPAS1 mutation (two-sided Fisher’s exact test). The square directs to a subset of patient samples used for WES (n = 68) in early ESCCs. Co-mutations: *p = 0.032 (TP53 and EPAS1), *p = 0.032 (TP53 and EPHA3), ****p = 9.3E–6 (EPAS1 and EPHA3). h Heatmap showing the phosphorylation of the phosphoproteins in cell–cell adhesion (Kruskal–Wallis test). The square directs to a subset of patient samples used for phosphoproteome (n = 119) in early ESCCs. ****p < 1.0E–4, ***p < 1.0E–3, **p < 0.01, *p < 0.05, ns. > 0.05. Source data are provided as a Source data file.