IBD-associated Colon Cancers Differ in DNA Methylation and Gene Expression Profiles Compared With Sporadic Colon Cancers.
DNA methylation
Ulcerative colitis
colon cancer
gene expression
inflammatory bowel disease
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
25 Jul 2019
25 Jul 2019
Historique:
pubmed:
13
2
2019
medline:
25
1
2020
entrez:
13
2
2019
Statut:
ppublish
Résumé
As ulcerative colitis [UC]-associated colorectal cancer [CRC] and sporadic CRC differ in presentation and molecular features, we sought to evaluate differences in the impact of DNA methylation on gene expression. DNA methylation was assessed in 11 UC-CRCs and adjacent tissue and 11 sporadic CRCs and adjacent tissue, using Illumina arrays. RNA sequencing was performed on 10 UC-CRCs and adjacent tissue and eight sporadic CRCs and adjacent tissues. Differences in DNA methylation and transcript expression, as well as their correlation in the same tissues, were assessed. Immunohistochemistry was performed for three proteins, ANPEP, FAM92A1, and STK31, all of which exhibited an inverse correlation between DNA methylation and transcript expression in UC. Thirty three loci demonstrated differences in DNA methylation between UC-CRC and adjacent tissue. In contrast, there were 4204 differentially methylated loci between sporadic colon cancer and adjacent tissue. Eight hundred eighty six genes as well as 10 long non-coding RNAs [lncRNA] were differentially expressed between UC-CRC and adjacent tissues. Although there were no differentially methylated loci between UC and sporadic CRC, 997 genes and 38 lncRNAs were differentially expressed between UC-CRC and sporadic CRC. In UC, 18 genes demonstrated a negative correlation between DNA methylation and transcript expression. Evaluation of protein expression related to three genes, ANPEP, FAM92A1, and STK31, confirmed down-regulation of ANPEP and up-regulation of STK31 in UC-CRC. Regulation of transcript expression by DNA methylation involves genes key to colon carcinogenesis and may account for differences in presentation and outcomes between inflammatory bowel disease and sporadic colon cancer.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
As ulcerative colitis [UC]-associated colorectal cancer [CRC] and sporadic CRC differ in presentation and molecular features, we sought to evaluate differences in the impact of DNA methylation on gene expression.
METHODS
METHODS
DNA methylation was assessed in 11 UC-CRCs and adjacent tissue and 11 sporadic CRCs and adjacent tissue, using Illumina arrays. RNA sequencing was performed on 10 UC-CRCs and adjacent tissue and eight sporadic CRCs and adjacent tissues. Differences in DNA methylation and transcript expression, as well as their correlation in the same tissues, were assessed. Immunohistochemistry was performed for three proteins, ANPEP, FAM92A1, and STK31, all of which exhibited an inverse correlation between DNA methylation and transcript expression in UC.
RESULTS
RESULTS
Thirty three loci demonstrated differences in DNA methylation between UC-CRC and adjacent tissue. In contrast, there were 4204 differentially methylated loci between sporadic colon cancer and adjacent tissue. Eight hundred eighty six genes as well as 10 long non-coding RNAs [lncRNA] were differentially expressed between UC-CRC and adjacent tissues. Although there were no differentially methylated loci between UC and sporadic CRC, 997 genes and 38 lncRNAs were differentially expressed between UC-CRC and sporadic CRC. In UC, 18 genes demonstrated a negative correlation between DNA methylation and transcript expression. Evaluation of protein expression related to three genes, ANPEP, FAM92A1, and STK31, confirmed down-regulation of ANPEP and up-regulation of STK31 in UC-CRC.
CONCLUSIONS
CONCLUSIONS
Regulation of transcript expression by DNA methylation involves genes key to colon carcinogenesis and may account for differences in presentation and outcomes between inflammatory bowel disease and sporadic colon cancer.
Identifiants
pubmed: 30753380
pii: 5315479
doi: 10.1093/ecco-jcc/jjz014
pmc: PMC7327274
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
884-893Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK042086
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA240710
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217078
Pays : United States
Informations de copyright
Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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