The top 20 mutated genes in the TCGA PAAD cohort were determined, which included KRAS (62%), TP53 (58%), SMAD4 (21%), CDKN2A (17%), TTN (14%), MUC16 (7%), RNF43 (6%), ARID1A (5%), HECW2 (5%) and RYR1 (5%), TGFBR2(5%), TNXB (5%), ATM (4%), CACNA1B (4%), FAT2 (4%), GLI3 (4%), GNAS (4%), LRP1B (4%), PCDH15 (4%) and RNF213 (4%) (Figure 2E). Here, SMAD4 is linked to pancreatic adenocarcinoma.