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

被引：28

作者：

Felix, Tainara F. ^{[1
,2
]}

Lopez Lapa, Rainer M. ^{[2
,3
]}

de Carvalho, Marcio ^{[4
]}

Bertoni, Natalia ^{[1
,2
]}

Tokar, Tomas ^{[5
]}

Oliveira, Rogerio A. ^{[6
]}

Rodrigues, Maria A. M. ^{[7
]}

Hasimoto, Claudia N. ^{[1
]}

Oliveira, Walmar K. ^{[1
]}

Pelafsky, Leonardo ^{[1
]}

Spadella, Cesar T. ^{[1
]}

Llanos, Juan C. ^{[1
]}

Silva, Giovanni F. ^{[8
]}

Lam, Wan L. ^{[9
]}

Rogatto, Silvia Regina ^{[10
]}

Amorim, Luciana Schultz ^{[11
]}

Drigo, Sandra A. ^{[1
,2
]}

Carvalho, Robson F. ^{[12
]}

Reis, Patricia P. ^{[1
,2
]}

机构：

[1] Sao Paulo State Univ UNESP, Fac Med, Dept Surg & Orthoped, Botucatu, SP, Brazil

[2] Sao Paulo State Univ UNESP, Fac Med, Expt Res Unity UNIPEX, Botucatu, SP, Brazil

[3] Sao Paulo State Univ UNESP, Inst Biosci, Dept Genet, Botucatu, SP, Brazil

[4] Sao Paulo State Univ UNESP, Sch Vet Med & Anim Sci, Dept Vet Clin, Botucatu, SP, Brazil

[5] Univ Hlth Network, Krembil Res Inst, Toronto, ON, Canada

[6] Sao Paulo State Univ UNESP, Inst Biosci, Dept Biostat, Botucatu, SP, Brazil

[7] Sao Paulo State Univ UNESP, Fac Med, Dept Pathol, Botucatu, SP, Brazil

[8] Sao Paulo State Univ UNESP, Fac Med, Dept Clin & Gastroenterol, Botucatu, SP, Brazil

[9] British Columbia Canc Ctr, Genet Unity, Integrat Oncol, Vancouver, BC, Canada

[10] Univ Southern Denmark, Vejle Hosp, Inst Reg Hlth Res, Dept Clin Genet, Odense, Denmark

[11] Inst Pathol Anat, Piracicaba, SP, Brazil

[12] Sao Paulo State Univ UNESP, Inst Biosci, Dept Morphol, Botucatu, SP, Brazil

来源：

PLOS ONE | 2019年 / 14卷 / 05期

基金：

巴西圣保罗研究基金会;

关键词：

NERVE GROWTH-FACTOR; CANCER; SUBTYPES; IMMUNOTHERAPY; INTERLEUKIN-6; LEUKOPLAKIA; COMPLEXITY; SIGNATURE; CARCINOMA; DATABASE;

D O I：

10.1371/journal.pone.0217421

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：20

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