Epigenome-Wide DNA Methylation Profiling of Normal Mucosa Reveals HLA-F Hypermethylation as a Biomarker Candidate for Serrated Polyposis Syndrome.
Journal
The Journal of molecular diagnostics : JMD
ISSN: 1943-7811
Titre abrégé: J Mol Diagn
Pays: United States
ID NLM: 100893612
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
15
10
2021
revised:
08
01
2022
accepted:
04
03
2022
pubmed:
22
4
2022
medline:
15
6
2022
entrez:
21
4
2022
Statut:
ppublish
Résumé
Serrated polyposis syndrome (SPS) is associated with a high risk for colorectal cancer. Intense promoter hypermethylation is a frequent molecular finding in the serrated pathway and may be present in normal mucosa, predisposing to the formation of serrated lesions. To identify novel biomarkers for SPS, fresh-frozen samples of normal mucosa from 50 patients with SPS and 19 healthy individuals were analyzed by using the 850K BeadChip Technology (Infinium). Aberrant methylation levels were correlated with gene expression using a next-generation transcriptome profiling tool. Two validation steps were performed on independent cohorts: first, on formalin-fixed, paraffin-embedded tissue of the normal mucosa; and second, on 24 serrated lesions. The most frequently hypermethylated genes were HLA-F, SLFN12, HLA-DMA, and RARRES3; and the most frequently hypomethylated genes were PIWIL1 and ANK3 (Δβ = 10%; P < 0.05). Expression levels of HLA-F, SLFN12, and HLA-DMA were significantly different between SPS patients and healthy individuals and correlated well with the methylation status of the corresponding differentially methylated region (fold change, >20%; r > 0.55; P < 0.001). Significant hypermethylation of CpGs in the gene body of HLA-F was also found in serrated lesions (Δβ = 23%; false discovery rate = 0.01). Epigenome-wide methylation profiling has revealed numerous differentially methylated CpGs in normal mucosa from SPS patients. Significant hypermethylation of HLA-F is a novel biomarker candidate for SPS.
Identifiants
pubmed: 35447336
pii: S1525-1578(22)00102-7
doi: 10.1016/j.jmoldx.2022.03.010
pmc: PMC9228001
pii:
doi:
Substances chimiques
Argonaute Proteins
0
Biomarkers
0
HLA-F antigens
0
Histocompatibility Antigens Class I
0
PIWIL1 protein, human
0
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
674-686Subventions
Organisme : NCI NIH HHS
ID : R01 CA072851
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA184792
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202797
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA187956
Pays : United States
Informations de copyright
Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Références
Gut. 2020 Jan;69(1):112-121
pubmed: 30981990
Epigenetics. 2018;13(10-11):1088-1105
pubmed: 30398409
Gut. 2017 Jul;66(7):1225-1232
pubmed: 26911398
Nat Rev Genet. 2011 Jul 12;12(8):529-41
pubmed: 21747404
Int J Cancer. 2013 Jan 1;132(1):82-9
pubmed: 22544725
Int J Oncol. 2012 Aug;41(2):490-6
pubmed: 22664866
Adv Genet. 2010;70:277-308
pubmed: 20920752
Oncol Lett. 2015 Jan;9(1):300-304
pubmed: 25435979
Int J Epidemiol. 2012 Feb;41(1):200-9
pubmed: 22422453
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Hum Pathol. 2010 Oct;41(10):1359-68
pubmed: 20594582
Immunity. 2017 Jun 20;46(6):1018-1029.e7
pubmed: 28636952
Nat Rev Genet. 2009 May;10(5):295-304
pubmed: 19308066
Clin Epigenetics. 2018 Nov 9;10(1):141
pubmed: 30413173
Gut. 2010 Aug;59(8):1094-100
pubmed: 19710031
Endoscopy. 2017 Jan;49(1):44-53
pubmed: 27741536
Nucleic Acids Res. 2013 Aug;41(14):6816-27
pubmed: 23748561
Gut. 2009 Jan;58(1):90-6
pubmed: 18832519
Am J Surg Pathol. 2002 Feb;26(2):249-56
pubmed: 11812948
Nucleic Acids Res. 2005 Nov 10;33(20):e175
pubmed: 16284200
Oncoimmunology. 2013 Nov 1;2(11):e26491
pubmed: 24482746
Cancers (Basel). 2019 Jul 20;11(7):
pubmed: 31330830
Gut Liver. 2017 Jan 15;11(1):38-46
pubmed: 27885175
Gastroenterol Rep (Oxf). 2014 Feb;2(1):16-20
pubmed: 24760232
Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):512-519
pubmed: 25587051
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Endoscopy. 2019 Sep;51(9):877-895
pubmed: 31342472
Lab Invest. 2015 Jul;95(7):833-42
pubmed: 25867767
Am J Surg Pathol. 2006 Dec;30(12):1491-501
pubmed: 17122504
Gut. 2012 Jun;61(6):847-54
pubmed: 22427238
Cancer Cell. 2013 Jul 8;24(1):15-29
pubmed: 23845441
Clin Epigenetics. 2016 Mar 02;8:25
pubmed: 26941852
Bioinformatics. 2014 Feb 01;30(3):428-30
pubmed: 24336642
Genome Biol. 2004;5(10):R80
pubmed: 15461798
J Cell Physiol. 2017 Nov;232(11):2938-2945
pubmed: 28112397
Dig Dis Sci. 2015 Mar;60(3):672-80
pubmed: 25492501
Br J Cancer. 2008 Jul 8;99(1):136-42
pubmed: 18542073
J Clin Oncol. 2004 Nov 15;22(22):4584-94
pubmed: 15542810
Cancer Lett. 2008 Feb 18;260(1-2):1-10
pubmed: 18164807
Gut. 2006 Oct;55(10):1467-74
pubmed: 16469793
Anal Cell Pathol (Amst). 2018 Oct 30;2018:7691704
pubmed: 30510890
Anticancer Res. 2015 Apr;35(4):2279-85
pubmed: 25862890
Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):111-130
pubmed: 31900466
Cell Oncol (Dordr). 2016 Jun;39(3):243-52
pubmed: 26832730
Oncogene. 2010 Mar 18;29(11):1653-62
pubmed: 19966864
Bioinformatics. 2017 Dec 15;33(24):3982-3984
pubmed: 28961746
Gastrointest Endosc. 2020 Nov;92(5):1098-1107.e1
pubmed: 32360902