Fig. 6: Newly identified APA-linked cancer susceptibility genes are enriched in metabolic reprogramming and apoptosis-related pathways.

APA-linked genes are connected in protein–protein interaction (PPI) networks with known cancer-risk genes, such as CASP8 in breast and skin cancer. Pathway enrichment analysis shows that 3′aTWAS genes are enriched in cancer-related pathways, including the metabolic reprogramming pathway like intracellular protein transport (P = 1.13 × 10−2, the apoptosis-related pathway (P = 8.75 × 10−4) and TRAIL signaling pathway (P = 6.07 × 10-4). Each node represents one APA-linked gene. Blue links between nodes represent a negative Z-score in 3′aTWAS, implying that usage of the short 3′UTR increases cancer risk, whereas red lines represent positive z-scores, indicating that usage of the longer 3′UTR leads to increased cancer risk. Gray dashed line indicated the PPI interactions between APA genes and the known cancer genes in CGC.