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:10.1371/journal.pone.0217421

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^*

^*Corresponding author for this work

Sao Paulo State University
University Health Network
BC Cancer Agency
Institute of Pathological Anatomy

Research output: Contribution to journal › Journal article › Research › peer-review

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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 (FC2 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.

Original language	English
Article number	e0217421
Journal	PLOS ONE
Volume	14
Issue number	5
Number of pages	20
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0217421
Publication status	Published - 31. May 2019

Funding

Funding:ResearchfundswereobtainedfromSão PauloResearchFoundation(FAPESP)(grant #2016/03905-2toP.P.Reis).T.F.F.wasfunded,in separatetimeperiods,throughtheCoordinationfor theImprovementofHigherLevelEducation (CAPES)andFAPESP-fellowship#2014/00367-4. Thefundershadnoroleinstudydesign,data

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Felix, T. F., Lopez Lapa, R. M., De Carvalho, M., Bertoni, N., Tokar, T., Oliveira, R. A., Rodrigues, M. A. M., Hasimoto, C. N., Oliveira, W. K., Pelafsky, L., Spadella, C. T., Llanos, J. C., Silva, G. F., Lam, W. L., Rogatto, S. R., Amorim, L. S., Drigo, S. A., Carvalho, R. F., & Reis, P. P. (2019). MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. PLOS ONE, 14(5), Article e0217421. https://doi.org/10.1371/journal.pone.0217421

@article{6da4a92e7b1445ee9826b43760794e84,

title = "MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma",

abstract = "Despite progress in treatment strategies, only \textasciitilde{}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 (FC2 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.",

author = "Felix, \{Tainara F.\} and \{Lopez Lapa\}, \{Rainer M.\} and \{De Carvalho\}, M{\'a}rcio and Nat{\'a}lia Bertoni and Tomas Tokar and Oliveira, \{Rog{\'e}rio A.\} and Rodrigues, \{Maria A.M.\} and Hasimoto, \{Cl{\'a}udia N.\} and Oliveira, \{Walmar K.\} and Leonardo Pelafsky and Spadella, \{C{\'e}sar T.\} and Llanos, \{Juan C.\} and Silva, \{Giovanni F.\} and Lam, \{Wan L.\} and Rogatto, \{Silvia Regina\} and Amorim, \{Luciana Schultz\} and Drigo, \{Sandra A.\} and Carvalho, \{Robson F.\} and Reis, \{Patricia P.\}",

year = "2019",

month = may,

day = "31",

doi = "10.1371/journal.pone.0217421",

language = "English",

volume = "14",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Felix, TF, Lopez Lapa, RM, De Carvalho, M, Bertoni, N, Tokar, T, Oliveira, RA, Rodrigues, MAM, Hasimoto, CN, Oliveira, WK, Pelafsky, L, Spadella, CT, Llanos, JC, Silva, GF, Lam, WL, Rogatto, SR, Amorim, LS, Drigo, SA, Carvalho, RF & Reis, PP 2019, 'MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma', PLOS ONE, vol. 14, no. 5, e0217421. https://doi.org/10.1371/journal.pone.0217421

TY - JOUR

T1 - MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma

AU - Felix, Tainara F.

AU - Lopez Lapa, Rainer M.

AU - De Carvalho, Márcio

AU - Bertoni, Natália

AU - Tokar, Tomas

AU - Oliveira, Rogério A.

AU - Rodrigues, Maria A.M.

AU - Hasimoto, Cláudia N.

AU - Oliveira, Walmar K.

AU - Pelafsky, Leonardo

AU - Spadella, César T.

AU - Llanos, Juan C.

AU - Silva, Giovanni F.

AU - Lam, Wan L.

AU - Rogatto, Silvia Regina

AU - Amorim, Luciana Schultz

AU - Drigo, Sandra A.

AU - Carvalho, Robson F.

AU - Reis, Patricia P.

PY - 2019/5/31

Y1 - 2019/5/31

N2 - 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 (FC2 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.

AB - 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 (FC2 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.

U2 - 10.1371/journal.pone.0217421

DO - 10.1371/journal.pone.0217421

M3 - Journal article

C2 - 31150430

AN - SCOPUS:85066448754

SN - 1932-6203

VL - 14

JO - PLOS ONE

JF - PLOS ONE

IS - 5

M1 - e0217421

ER -

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

Abstract

Funding

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