title: Differential Expression of MicroRNAs in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer.
abstract: OBJECTIVE
  Pancreatic cancer (PC) is a lethal disease with disappointing results from current treatment modalities, suggesting that novel therapeutic strategies are urgently needed. Since microRNAs (miRNAs) are important player in biology, the clinical utility of miRNAs for designing novel therapeutics is an active area of research. The objective of the present study was to examine differentially expressed miRNAs between normal and tumor tissues, and in plasma samples obtained from PC patients, chronic pancreatitis (CP) patients and healthy subjects (HC).
  
  
  METHODS
  The miRNA expression profiling using formalin-fixed paraffin embedded (FFPE) tissues from normal and tumor specimens was accomplished using miRBase version 19 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was subsequently performed in individual samples for 7 selected miRNAs. In addition, qRT-PCR was also performed for assessing the expression of 8 selected miRNAs in plasma samples.
  
  
  RESULTS
  A significant difference in the expressions ofmiR-21, miR-205, miR-155, miR-31, miR-203, miR-214andmiR-129-2were found in tumor tissue samples. Lower expression ofmiR-214was found to be associated with better overall survival. We also observed differential expression of 8 miRNAs in plasma samples of CP and PC patients compared to HC. Interestingly, over expression ofmiR-21, andmiR-31was noted in both tumor tissues and in the plasma.
  
  
  CONCLUSIONS
  We found deregulated expression of miRNAs that could distinguish normal from PC in two different types of samples (tissues and plasma). Interestingly, lower expression ofmiR-214was found to be associated with better overall survival. Although not statistically significant, we also observed higher expression oflet-7aand lower expression ofmiR-508to be associated with overall better survival. We conclude that our study nicely lays the foundation for detailed future investigations for assessing the role of these miRNAs in the pathology of pancreatic cancer.
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Shadan
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Hala
authors.initials: H
authors.lastname: Dubaybo
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA; Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
keywords: Chronic Pancreatitis; FFPE; Pancreatic Cancer; Plasma; miRNAs; qRT-PCR
references.citation: PLoS One. 2015 Jul 28;10(7):e0133643
references.pmid: 26218285
references.citation: Ann Surg Oncol. 2010 Dec;17(12):3120-8
references.pmid: 20652642
references.citation: Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):5-8
references.pmid: 20005451
references.citation: Cancer Cell Int. 2013 Jul 08;13(1):68
references.pmid: 23834902
references.citation: Front Cell Dev Biol. 2014 Oct 16;2:61
references.pmid: 25364765
references.citation: JAMA. 2007 May 2;297(17):1901-8
references.pmid: 17473300
references.citation: Cancer Res. 2015 Oct 15;75(20):4384-97
references.pmid: 26249174
references.citation: Dig Dis Sci. 2014 Jul;59(7):1452-60
references.pmid: 24532253
references.citation: Clin Lab Med. 2013 Dec;33(4):773-86
references.pmid: 24267185
references.citation: J Gastroenterol Hepatol. 2005 Oct;20(10 ):1591-4
references.pmid: 16174079
references.citation: Arch Biochem Biophys. 2015 Aug 15;580:84-92
references.pmid: 26151775
references.citation: J Clin Med. 2015 Aug 06;4(8):1566-77
references.pmid: 26258795
references.citation: Br J Cancer. 2012 Oct 9;107(8):1354-60
references.pmid: 22929886
references.citation: J Surg Res. 2009 Jun 15;154(2):349-54
references.pmid: 18656897
references.citation: Cancer Sci. 2015 Oct;106(10):1362-9
references.pmid: 26195069
references.citation: PLoS One. 2014 Sep 03;9(9):e106343
references.pmid: 25184537
references.citation: Biometals. 2015 Oct;28(5):879-90
references.pmid: 26209160
references.citation: Expert Rev Mol Diagn. 2014 Apr;14(3):267-71
references.pmid: 24575833
references.citation: J Clin Med. 2015 Jul 07;4(7):1369-79
references.pmid: 26239681
references.citation: Gene. 2015 Dec 10;574(1):163-7
references.pmid: 26253160
references.citation: Am J Cancer Res. 2013 Nov 01;3(5):465-77
references.pmid: 24224124
references.citation: Cancer Lett. 2014 Aug 28;351(1):151-61
references.pmid: 24880079
references.citation: Diagn Pathol. 2015 Apr 24;10:38
references.pmid: 25908274
references.citation: Cancer Prev Res (Phila). 2012 Mar;5(3):355-64
references.pmid: 22086681
references.citation: Nan Fang Yi Ke Da Xue Xue Bao. 2015 Aug;35(8):1110-5
references.pmid: 26277505
references.citation: Medicine (Baltimore). 2015 Mar;94(10):e603
references.pmid: 25761179
references.citation: Oncol Rep. 2013 Sep;30(3):1223-30
references.pmid: 23817566
references.citation: Cancer Res. 2012 Jan 1;72 (1):335-45
references.pmid: 22108826
references.citation: Am J Cancer Res. 2015 Feb 15;5(3):1251-64
references.pmid: 26046003
references.citation: Clin Cancer Res. 2015 Aug 1;21(15):3512-21
references.pmid: 26240291
references.citation: J Gastrointest Surg. 2013 Aug;17 (8):1399-405
references.pmid: 23715647
references.citation: J Cancer Sci Ther. 2015 May;7(5):145-154
references.pmid: 26380656
references.citation: Nat Commun. 2014 Aug 06;5:4620
references.pmid: 25099196
references.citation: Genes Chromosomes Cancer. 2012 Jun;51(6):557-68
references.pmid: 22344632
references.citation: Target Oncol. 2015 Dec;10 (4):535-48
references.pmid: 25639539
references.citation: PLoS One. 2012;7(12):e48637
references.pmid: 23251334
references.citation: CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29
references.pmid: 24399786
references.citation: J Exp Clin Cancer Res. 2013 Sep 28;32:71
references.pmid: 24289824
references.citation: J Cancer. 2014 Sep 16;5(8):696-705
references.pmid: 25258651
references.citation: PLoS One. 2013;8(1):e53436
references.pmid: 23335963
references.citation: Am J Transl Res. 2010 Sep 28;3(1):28-47
references.pmid: 21139804
references.citation: Oncotarget. 2015 Aug 28;6(25):21148-58
references.pmid: 26020803
references.citation: Cancer Lett. 2015 Jan 28;356(2 Pt B):404-9
references.pmid: 25304377
references.citation: Ann Surg Treat Res. 2014 Dec;87(6):290-7
references.pmid: 25485236
references.citation: JAMA. 2014 Jan 22-29;311(4):392-404
references.pmid: 24449318