Fig. 2: The risk factor-associated mutational signatures in ESCC progression.

a Heatmap showing the significantly positive associated mutations in SBS16 signature (two-sided Fisher’s exact test). ***p = 1.4E–4 (BCKDK), **p = 2.7E–3 (CEP104), ***p = 1.4E–4 (LRRC31), ***p = 4.5E–4 (OLFM4), ***p = 1.5E–3 (DSC3), ***p = 1.5E–3 (PGC). The square directs to a subset of patient samples used for WES. b Volcano analysis of the impacts of significantly positive associated mutations in SBS16 signature on their counterpart proteins expression (two-sided Wilcoxon signed-rank test). c Represented pathway enrichment that was positively correlated with OLFM4. d Heatmap showing the protein levels of DNA replication in OLFM4 mutation group vs. WT group (two-sided Wilcoxon signed-rank test, BH-adjusted *p < 0.05). e The expression (log₂-transformed Intensity, median) of represented DNA replication-related phosphoprotein in ESCC progression (Kruskal–Wallis test, BH-adjusted *p < 0.05). A total of 145 samples for phosphoproteomic profiling are used in this analysis. n (NT) = 57, n (IEN) = 62, n (A-ESCC) = 26 biologically independent samples examined. f The correlation between etiological factors (top) and the significantly associated mutations of APOBEC signature (bottom) (two-sided Fisher’s exact test). *p = 0.012 (Phase), **p = 4.2E–3 (Habit), **p = 4.6E–3 (DCTN2), **p = 4.6E–3 (EPS8), **p = 4.6E–3 (CENPE). g Venn diagram depicting the number of the overlapped proteins overrepresented in the APOBEC signature and non-smoking/drinking ESCC patients (left, two-sided Wilcoxon signed-rank test, BH-adjusted *p < 0.05), and the associated signaling pathways (right). h Venn plot (left) showing the overlapped proteins significantly correlated with DCTN2 at the gene and protein levels (two-sided Wilcoxon signed-rank test, BH-adjusted *p < 0.05). Volcano plot (right) depicting the correlation between DCTN2 and the overlapped proteins (n = 86, two-sided Pearson’s correlation test). i Heatmap (left) presenting the represented chromosomal/spindle components and cell proliferation markers overrepresented in the DCTN2 mutation group (two-sided Wilcoxon signed-rank test), and correlation (right) between DCTN2/RUVBL1 and represented chromosomal/spindle components and cell proliferation markers (two-sided Pearson’s correlation test). j A brief summary of the impacts of the SBS16 signature (top) and APOBEC signature (bottom) in ESCC progression. A total of 102 samples for WES are used in the analysis. ****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.