title: Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor.
abstract: Diagnostic markers are needed for achieving a cure in esophageal cancer, detecting tumor cells earlier. Exosomes are bioactive vesicles secreted by cells into surrounding body fluids. Exosome formation, cargo content, and delivery have major impact in cancer development. This is the first isolation of exosomes from serum of patients with adenocarcinoma of the esophagus and comparison of exosomal miRNA profiles with matching primary tumor and normal tissues. RNA was extracted for miRNA profiling by real-time TaqMan miR arrays. The miR profiles of exosomal cargo, matching tumor, and normal tissue of a subgroup of adenocarcinoma patients have been compared. "Exosomal onco-miRs" such as miR-223-5p, miR-223-3p, miR-483-5p, miR-409-3p, miR-196b-5p, miR-192-5p, miR-146a-5p, and miR-126-5p have been identified as part of exosomal cargo being overexpressed in corresponding tumor compared to normal. Upregulation of miR-223-5p and miR-483-5p in adenocarcinoma (p = 0.034, p = 0.017) has been verified by an independent cohort of 43 patients with T2-3 adeno- and squamous cell carcinoma. In contrast, miR-224-5p, miR-452-5p, miR-23b-5p, miR-203-5p, miR-1201-5p, miR-149-5p, miR-671-3p, miR-944-5p, miR-27b-3p, and miR-22-3p have been identified to be significantly downregulated in adenocarcinoma versus normal and merely or not detectable in exosomes. "Exosomal onco-miRs" are a novel, stable, and noninvasive source for diagnosis and therapy monitoring of esophageal cancer. Oncogenic shuttle miRNAs present in exosomes may contribute to understanding how tumor cells spread their oncogenic potential to the environment. The "exosomal onco-miRs" identified seem to play a major role and may be applied for noninvasive diagnosis and therapy monitoring of adenocarcinoma of the esophagus.
authors: General, Visceral and Cancer Surgery, University Hospital of Cologne, Kerpener Straße 62, D-50937, Cologne, Germany, ute.warnecke-eberz@uk-koeln.de.
authors: Ute
authors: U
authors: Warnecke-Eberz
authors: Seung-Hun
authors: SH
authors: Chon
authors: Arnulf H
authors: AH
authors: Hölscher
authors: Uta
authors: U
authors: Drebber
authors: Elfriede
authors: E
authors: Bollschweiler
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D004938:Esophageal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D055354:Exosomes / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
references: Br J Cancer. 2013 Feb 19;108(3):644-52
references: 23361059
references: Ann Oncol. 2012 Dec;23(12):3155-62
references: 22847812
references: Diagn Pathol. 2013 Apr 30;8:69
references: 23631806
references: Cancer. 2013 Mar 15;119(6):1159-67
references: 23224754
references: Cancer. 2011 Apr 15;117(8):1630-9
references: 21472710
references: Nat Cell Biol. 2007 Jun;9(6):654-9
references: 17486113
references: PLoS One. 2012;7(7):e41629
references: 22860003
references: Semin Cancer Biol. 2012 Aug;22(4):342-9
references: 22369922
references: J Biomed Sci. 2011 Mar 31;18:24
references: 21453483
references: Biomed Rep. 2013 Nov;1(6):907-912
references: 24649051
references: Cancer. 2001 Aug 1;92(3):549-55
references: 11505399
references: Nature. 2005 Jun 9;435(7043):834-8
references: 15944708
references: Clin Cancer Res. 2012 Sep 15;18(18):4919-30
references: 22850566
references: Chin J Cancer Res. 2014 Feb;26(1):95-103
references: 24653631
references: PLoS One. 2014 Mar 20;9(3):e92292
references: 24651474
references: Cancer Res. 2014 Jun 1;74(11):3031-42
references: 24710410
references: Cancer Lett. 2012 Jul 28;320(2):189-97
references: 22388101
references: Cancer Lett. 2012 Oct 28;323(2):171-9
references: 22531314
references: Int J Cancer. 2014 Aug 1;135(3):541-50
references: 24382668
references: PLoS One. 2013 Jul 29;8(7):e68744
references: 23922662
references: Curr Pharm Des. 2013;19(7):1292-300
references: 23092349
references: J Cancer Res Clin Oncol. 2012 May;138(5):763-74
references: 22270966
references: Oncol Rep. 2012 Nov;28(5):1551-8
references: 22895844
references: Mol Cancer. 2011 Sep 22;10:117
references: 21939504
references: Pathol Oncol Res. 2014 Apr;20(2):245-52
references: 24519530
references: Genes Chromosomes Cancer. 2014 Oct;53(10):881
references: 24898922
references: Br J Cancer. 2014 Jun 10;110(12):2945-54
references: 24823697
references: Trends Cell Biol. 2008 May;18(5):199-209
references: 18396047
references: PLoS One. 2013 Apr 12;8(4):e60687
references: 23593282
references: N Engl J Med. 2012 May 31;366(22):2074-84
references: 22646630
references: Clin Cancer Res. 2009 Nov 15;15(22):6830-40
references: 19861441
references: J Extracell Vesicles. 2013 Jun 18;2:null
references: 24009888
references: PLoS One. 2013 May 28;8(5):e64463
references: 23724052
references: Carcinogenesis. 2012 Jun;33(6):1126-33
references: 22491715
references: Asian Pac J Cancer Prev. 2014;15(4):1675-9
references: 24641388
references: Future Oncol. 2010 Jan;6(1):25-35
references: 20021207
references: Lancet Oncol. 2008 Aug;9(8):808
references: 18672217
references: Oncol Lett. 2013 May;5(5):1639-1642
references: 23761828