Microrna Modulated Networks Of Adaptive And Innate Immune Response In Pancreatic Ductal Adenocarcinoma

Despite progress in treatment strategies, only similar to 24% of pancreatic ductal adenocarcinoma (PDAC) patients survive > 1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC >= 2 and p< 0.05) (15 down-and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down-and 1 up-regulated miRNAs (FDR p< 0.05). Most enriched pathways (p< 0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.