Cell-free DNA 5-hydroxymethylcytosine is an emerging marker of acute myeloid leukemia.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 07 2022
20 07 2022
Historique:
received:
28
09
2021
accepted:
13
07
2022
entrez:
20
7
2022
pubmed:
21
7
2022
medline:
23
7
2022
Statut:
epublish
Résumé
Aberrant changes in 5-hydroxymethylcytosine (5hmC) are a unique epigenetic feature in many cancers including acute myeloid leukemia (AML). However, genome-wide analysis of 5hmC in plasma cell-free DNA (cfDNA) remains unexploited in AML patients. We used a highly sensitive and robust nano-5hmC-Seal technology and profiled genome-wide 5hmC distribution in 239 plasma cfDNA samples from 103 AML patients and 81 non-cancer controls. We developed a 5hmC diagnostic model that precisely differentiates AML patients from controls with high sensitivity and specificity. We also developed a 5hmC prognostic model that accurately predicts prognosis in AML patients. High weighted prognostic scores (wp-scores) in AML patients were significantly associated with adverse overall survival (OS) in both training (P = 3.31e-05) and validation (P = 0.000464) sets. The wp-score was also significantly associated with genetic risk stratification and displayed dynamic changes with varied disease burden. Moreover, we found that high wp-scores in a single gene, BMS1 and GEMIN5 predicted OS in AML patients in both the training set (P = 0.023 and 0.031, respectively) and validation set (P = 9.66e-05 and 0.011, respectively). Lastly, our study demonstrated the genome-wide landscape of DNA hydroxymethylation in AML and revealed critical genes and pathways related to AML diagnosis and prognosis. Our data reveal plasma cfDNA 5hmC signatures as sensitive and accurate markers for AML diagnosis and prognosis. Plasma cfDNA 5hmC analysis will be an effective and minimally invasive tool for AML management.
Identifiants
pubmed: 35859008
doi: 10.1038/s41598-022-16685-3
pii: 10.1038/s41598-022-16685-3
pmc: PMC9300744
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
5-hydroxymethylcytosine
1123-95-1
5-Methylcytosine
6R795CQT4H
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12410Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG006827
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560
pubmed: 31114875
Nature. 2010 Dec 9;468(7325):839-43
pubmed: 21057493
Leukemia. 2021 Jul;35(7):1873-1889
pubmed: 33958699
N Engl J Med. 2013 May 30;368(22):2059-74
pubmed: 23634996
Cancer Cell. 2010 Dec 14;18(6):553-67
pubmed: 21130701
Science. 2009 May 15;324(5929):930-5
pubmed: 19372391
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
Leukemia. 2011 Oct;25(10):1649-52
pubmed: 21625234
Nat Med. 2008 Sep;14(9):985-90
pubmed: 18670422
Nat Commun. 2017 Mar 17;8:14756
pubmed: 28303898
Int J Mol Sci. 2019 Sep 16;20(18):
pubmed: 31527484
Blood Rev. 2017 Jan;31(1):63-76
pubmed: 27639498
Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):264-269
pubmed: 30504320
Cell Res. 2017 Oct;27(10):1243-1257
pubmed: 28925386
Blood. 2017 Mar 23;129(12):1685-1690
pubmed: 28126926
Gut. 2019 Dec;68(12):2195-2205
pubmed: 31358576
Signal Transduct Target Ther. 2020 Jan 10;5(1):3
pubmed: 32296024
Haematologica. 2015 Jul;100(7):e280-4
pubmed: 25749829
Cancers (Basel). 2019 Dec 31;12(1):
pubmed: 31906064
Haematologica. 2018 Mar;103(3):e115-e118
pubmed: 29242297
Eur J Haematol. 2017 Oct;99(4):291-299
pubmed: 28692178
Nucleic Acids Res. 2018 Aug 21;46(14):7339-7353
pubmed: 29771365
Histopathology. 2016 Dec;69(6):1055-1065
pubmed: 27458708
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Genome Biol. 2014;15(12):550
pubmed: 25516281
Oncotarget. 2017 Jan 31;8(5):8305-8314
pubmed: 28039446
Cold Spring Harb Perspect Med. 2017 Aug 1;7(8):
pubmed: 28242787
Leuk Lymphoma. 2013 Nov;54(11):2466-73
pubmed: 23432690
BMC Genomics. 2014 Apr 15;15:284
pubmed: 24735413
Haematologica. 2016 Sep;101(9):997-9
pubmed: 27582567
Br J Haematol. 1994 Apr;86(4):774-9
pubmed: 7918071
Biochem Biophys Res Commun. 2012 Mar 23;419(4):662-9
pubmed: 22382018
Blood. 2019 Jun 20;133(25):2682-2695
pubmed: 30936070
Cancer Commun (Lond). 2019 Mar 29;39(1):12
pubmed: 30922396
Trends Biochem Sci. 2017 Dec;42(12):977-989
pubmed: 29122461
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
Cancer Sci. 2016 Sep;107(9):1329-37
pubmed: 27323954
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Leukemia. 2018 Aug;32(8):1838-1841
pubmed: 29749395
J Genet Genomics. 2012 Sep 20;39(9):451-62
pubmed: 23021545
Mol Cell. 2016 Aug 18;63(4):711-719
pubmed: 27477909
Blood. 2014 Aug 14;124(7):1110-8
pubmed: 24986689
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Genet Test Mol Biomarkers. 2016 Jul;20(7):341-5
pubmed: 27248906
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Mol Oncol. 2021 Jan;15(1):138-150
pubmed: 33107199
Nat Commun. 2020 Dec 2;11(1):6161
pubmed: 33268789
Nat Chem. 2014 Dec;6(12):1049-55
pubmed: 25411882
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Int J Med Sci. 2015 Jan 01;12(1):17-22
pubmed: 25552914
Nat Commun. 2020 Oct 19;11(1):5270
pubmed: 33077732
Blood Adv. 2019 Oct 8;3(19):2790-2799
pubmed: 31570490
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278