Fig. 3: Fuels of transcriptomic ITH in ESCC.

a RNA intertumor (x-axis) and RNA intratumor heterogeneity (y-axis) are shown on the axes using density curves. The genes are split into four classes by the mean intratumor and intertumor heterogeneity scores. The classes are numbered and colored. b Boxplots show the clustering concordance score per gene in each class (I = 3354 genes, II = 11622 genes, III = 5368 genes, IV = 3668 genes). The minimum and maximum are indicated by the extremes of the box plot; the median is indicated by the thick horizontal line; and the first and third quartiles are indicated by box edges; *P < 0.05, **P < 0.01, two-sided Wilcoxon rank-sum test. c Correlation of gene expression ITH with copy-number ITH. The Spearman correlation coefficient (Rs) between patient-wise RNA-ITH scores and patient-wise SCNA-ITH scores calculated in the ESCC cohort (n = 33 ESCC patients; Rs = 0.38; P = 0.027). Line of best fit shown in orange and gray area represents 95% confidence bands. d Violin boxplots show the correlation between subclonal chromosomal copy-number changes and gene expression across 36 ESCC patients. The minimum and maximum are indicated by the extremes of the box plot; the median is indicated by the thick horizontal line; and the first and third quartiles are indicated by box edges; two-sided Wilcoxon rank-sum test. e All the genes were classified in clonal/subclonal gain, loss, or no change types. Enrichment was tested by RNA heterogeneity class. Odds ratios are shown using a natural log scale. A two-sided Fisher’s exact test was performed. f The spearman correlation between patient-wise RNA-ITH and methylation of promoter regions calculated in the 36 ESCC cohort. Spearman’s correlation coefficient (Rs) and corresponding P-value are shown. Line of best fit shown in brown and gray area represents 95% confidence bands.