Fig. 2: Discrete profile of intronic APA events in TCGA data.

a A workflow depicting the pan-cancer data analyses for intronic APA events. b Differential expression analyses of genes with annotated intronic APA events in normal tissues and tumor samples. Three representative TCGA datasets (TCGA-BRCA (breast invasive carcinoma), TCGA-KIRC (kidney renal clear cell carcinoma), and TCGA-LUAD (lung adenocarcinoma)) are shown. The x-axis shows the significance of intronic APA events calculated using −log₁₀(p value), whereas the y-axis shows the fold changes in gene expression in tumors compared with normal samples. Red dots indicate the genes showing significant intronic APA events conserved in 80% or more of tumor samples (i.e., 80% or more of tumor samples have higher TRs than the mean TR of normal tissue samples). The blue dots indicate the genes showing significant APA events for which 80% or more of the tumor samples had TRs lower than the mean TR of the normal tissue samples. c H2AZ2 and LRRFIP1 genes showing intronic APA events in BRCA tumors are presented as examples. The left panel displays the expression profiles of intronic APA (int APA; red) and full-length (FL; blue) transcripts across tumor samples and normal tissues. The middle panel presents the TRs of the corresponding genes in an individual sample using a box plot. The cyan bar indicates the median TR in tumor and normal samples. The right panel shows the distribution of H2AZ2 and LRRFIP1 TRs across the samples. The fraction of samples indicates the percentage of tumors that display a higher TR compared to the median of TR in the normal samples or vice versa. d CXCL12 and DST genes showing intronic APA events in normal tissues in BRCA are presented as examples. Each panel shows the same data analyses as described in (c). e Scatter plots for intronic APA events in BRCA, KIRC, and LUAD. The TR means for genes with significant intronic APA events are color-coded. Genes showing intronic APA events in more than 88% of the samples are color-coded as blue (normal) or red (tumor). Genes with intronic APA events in 80−88% of the samples are shown in cyan (normal) or orange (tumor). f Overall distribution of intronic APA events in the TCGA pan-cancer cohort and corresponding normal tissue data. g Heatmap of the KEGG pathways enriched in intronic APA events across 10 cancer types. The KEGG pathways that are common to two or more cancers are displayed. The color scale represents −log₁₀(p value) for pathways enriched in tumors and log₁₀(p value) for pathways enriched in normal tissues: red-colored KEGG pathways are enriched in tumor samples, and blue-colored KEGG pathways are enriched in normal tissues. h Significant intronic APA genes associated with the ribosome or oxidative phosphorylation pathway in tumor samples according to the pan-cancer data. The scale of the circle indicates [the TR mean in tumors]/[the TR mean in normal tissues]. i Significant intronic APA genes associated with the cell cycle or focal adhesion pathways in normal tissues according to the pan-cancer data. The scale of the circle indicates [the TR mean in normal tissues]/[the TR mean in tumors].