PLoS ONE (Jan 2019)

MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma.

  • Tainara F Felix,
  • Rainer M Lopez Lapa,
  • Márcio de Carvalho,
  • Natália Bertoni,
  • Tomas Tokar,
  • Rogério A Oliveira,
  • Maria A M Rodrigues,
  • Cláudia N Hasimoto,
  • Walmar K Oliveira,
  • Leonardo Pelafsky,
  • César T Spadella,
  • Juan C Llanos,
  • Giovanni F Silva,
  • Wan L Lam,
  • Silvia Regina Rogatto,
  • Luciana Schultz Amorim,
  • Sandra A Drigo,
  • Robson F Carvalho,
  • Patricia P Reis

DOI
https://doi.org/10.1371/journal.pone.0217421
Journal volume & issue
Vol. 14, no. 5
p. e0217421

Abstract

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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.