title: Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease.
abstract: Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and predictive blood biomarkers for aGVHD in clinical use. Here, we show that plasma samples from aGVHD patients have a distinct microRNA (miRNA) expression profile. We found that 6 miRNAs (miR-423, miR-199a-3p, miR-93*, miR-377, miR-155, and miR-30a) were significantly upregulated in the plasma of aGVHD patients (n = 116) when compared with non-GVHD patients (n = 52) in training and validation phases. We have developed a model including 4 miRNAs (miR-423, miR-199a-3p, miR-93*, and miR-377) that can predict the probability of aGVHD with an area under the curve of 0.80. Moreover, these elevated miRNAs were detected before the onset of aGVHD (median = 16 days before diagnosis). In addition, the levels of these miRNAs were positively associated with aGVHD severity, and high expression of the miRNA panel was associated with poor overall survival. Furthermore, the miRNA signature for aGVHD was not detected in the plasma of lung transplant or nontransplant sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as an independent biomarker for the prediction, diagnosis, and prognosis of aGVHD.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC;
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Megan
authors.initials: M
authors.lastname: Baker
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.forename: Kelly
authors.initials: K
authors.lastname: Corbet
authors.forename: Ephraim L
authors.initials: EL
authors.lastname: Tsalik
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Woods
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D019337:Hematologic Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
references.citation: Clin Chem. 2009 Nov;55(11):1944-9
references.pmid: 19696117
references.citation: Blood. 2009 Jan 8;113(2):273-8
references.pmid: 18832652
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8
references.pmid: 21383194
references.citation: Blood. 2013 Jan 24;121(4):585-94
references.pmid: 23165480
references.citation: Int Rev Immunol. 2009;28(5):264-84
references.pmid: 19811312
references.citation: Cancer Cell. 2011 Feb 15;19(2):232-43
references.pmid: 21316602
references.citation: Hepatology. 2011 Nov;54(5):1767-76
references.pmid: 22045675
references.citation: Hepatology. 2013 Feb;57(2):840-7
references.pmid: 23081718
references.citation: Gut. 2009 Oct;58(10):1375-81
references.pmid: 19201770
references.citation: Circ Res. 2010 Apr 2;106(6):1035-9
references.pmid: 20185794
references.citation: Circ Res. 2010 Sep 17;107(6):810-7
references.pmid: 20651284
references.citation: Cancer Res. 2010 Dec 1;70(23):9798-807
references.pmid: 21098710
references.citation: Nat Rev Immunol. 2012 May 11;12(6):443-58
references.pmid: 22576252
references.citation: Bone Marrow Transplant. 1998 Jan;21(1):29-32
references.pmid: 9486491
references.citation: Cancer Sci. 2010 Oct;101(10):2087-92
references.pmid: 20624164
references.citation: PLoS One. 2009 Oct 12;4(10):e7405
references.pmid: 19823581
references.citation: Lancet. 2009 May 2;373(9674):1550-61
references.pmid: 19282026
references.citation: Clin Chem. 2010 Nov;56(11):1733-41
references.pmid: 20847327
references.citation: Clin Chem. 2013 Aug;59(8):1175-86
references.pmid: 23592504
references.citation: Blood. 2013 Jun 20;121(25):4977-84
references.pmid: 23550041
references.citation: Bone Marrow Transplant. 1998 Apr;21(8):769-73
references.pmid: 9603399
references.citation: Nat Cell Biol. 2011 Apr;13(4):423-33
references.pmid: 21423178
references.citation: Blood. 2011 Nov 17;118(20):5487-97
references.pmid: 21972292
references.citation: Gastroenterology. 2012 May;142(5):1206-1217.e7
references.pmid: 22265968
references.citation: Blood. 2007 May 15;109(10):4119-26
references.pmid: 17234737
references.citation: Bone Marrow Transplant. 1995 Jun;15(6):825-8
references.pmid: 7581076
references.citation: Circ Cardiovasc Genet. 2011 Aug 1;4(4):446-54
references.pmid: 21642241
references.citation: J Virol. 2008 Aug;82(16):8215-23
references.pmid: 18550664
references.citation: Nat Cell Biol. 2007 Jun;9(6):654-9
references.pmid: 17486113
references.citation: Blood. 2012 May 17;119(20):4786-97
references.pmid: 22408260
references.citation: Blood. 2008 Apr 15;111(8):4403-12
references.pmid: 18256320
references.citation: Exp Hematol. 2006 Jun;34(6):796-801
references.pmid: 16728285
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Circulation. 2011 Oct 4;124(14):1537-47
references.pmid: 21900086
references.citation: Nature. 2005 Jul 14;436(7048):214-20
references.pmid: 15951802
references.citation: Cell Res. 2008 Oct;18(10):997-1006
references.pmid: 18766170
references.citation: Nucleic Acids Res. 2010 Nov;38(20):7248-59
references.pmid: 20615901
references.citation: Blood. 2006 May 15;107(10):4177-81
references.pmid: 16449522
references.citation: J Biol Chem. 2012 Feb 3;287(6):4148-56
references.pmid: 22157765
references.citation: Clin Chem. 2012 May;58(5):896-905
references.pmid: 22395025
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8
references.pmid: 18663219
references.citation: PLoS Genet. 2012;8(6):e1002751
references.pmid: 22685420
references.citation: Am J Transplant. 2013 Jan;13(1):11-9
references.pmid: 23136949
references.citation: Br J Haematol. 2013 Feb;160(3):288-302
references.pmid: 23205489
references.citation: Carcinogenesis. 2012 Apr;33(4):732-9
references.pmid: 22287560