Abstract
Despite progress in treatment strategies, only ~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-216a-5p, 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.
Highlights
Pancreatic cancer is the fourth most frequent cause of cancer death, worldwide [1,2]
Our study shows that PDAC and AMP display different global miRNA expression profiles, which reflect distinct miRNA-regulated networks and pathways of tumorigenesis
We identified 20 significantly deregulated miRNAs (FC 2 and p
Summary
Pancreatic cancer is the fourth most frequent cause of cancer death, worldwide [1,2]. AMP patients have a better prognosis (5-year survival of >45%) [3,4] compared to PDAC, mainly due to early disease detection. The asymptomatic nature of PDAC is often associated with late diagnosis and poor patient prognosis. This disease is characterized by very aggressive and rapid tumor growth and high incidence of distant metastasis [5]. Despite progress in treatment strategies (surgery, chemo and radiation therapies) in the past 5 years, only 24% of patients with PDAC survive more than a year and
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