Activation of transposable elements in PAAD. (A) Overview of the data sets used in this study, including both in-house and publicly available data. Detailed numbers for each data type are provided (top panel). The schematic illustrates the activation of promoters within transposable elements (TEs) in PAAD. Upon activation, these promoters may drive onco-exaptation, resulting in the expression of chimeric transcripts that contribute to oncogenesis, or generate neoantigens that trigger an immune response (bottom panel). (B) Volcano plot showing the differentially expressed TE loci in tumor organoid and normal organoid. The TE-IDs such as “AluYm1_dup3579” were listed in Supplemental Table S2. Only genes with FDR-adjusted P-values < 0.05 and absolute log2 fold change of ≥4 are considered significantly differentially expressed. (C) Oncoprint illustrating drug sensitivity, driver gene mutations, tumor biomarker levels, and survival outcomes of patients who underwent organoid-based drug screening. (D) Comparison of ATAC-seq signals located within 3 kb upstream of and downstream from DETEs between organoid tumor and normal samples. Unchanged TE regions (2000 randomly selected) were used as a control. Statistical analysis was performed using the Wilcoxon test, with a P-value < 0.05 considered statistically significant. PAAD tumor organoid, n = 62; Normal organoid, n = 5. (E) Gene Ontology (GO) enrichment analysis of biological processes associated with DETEs in PAADs.
