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PLoS One. 2019 May 31;14(5):e0217421. doi: 10.1371/journal.pone.0217421. eCollection 2019.

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

Author information

1
Department of Surgery and Orthopedics, Faculty of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil.
2
Experimental Research Unity (UNIPEX), Faculty of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil.
3
Department of Genetics, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, SP, Brazil.
4
Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
5
Krembil Research Institute, University Health Network, Toronto, ON, Canada.
6
Department of Biostatistics, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, SP, Brazil.
7
Department of Pathology, Faculty of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil.
8
Department of Clinics and Gastroenterology, Faculty of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil.
9
Genetics Unity, Integrative Oncology, British Columbia Cancer Center, Vancouver, BC, Canada.
10
Department of Clinical Genetics, Vejle Hospital, Institute of Regional Health Research, University of Southern Denmark, Denmark, DK.
11
Institute of Pathological Anatomy, Piracicaba, SP, Brazil.
12
Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, SP, Brazil.

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.

PMID:
31150430
DOI:
10.1371/journal.pone.0217421
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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