Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer.
Journal
Cancer prevention research (Philadelphia, Pa.)
ISSN: 1940-6215
Titre abrégé: Cancer Prev Res (Phila)
Pays: United States
ID NLM: 101479409
Informations de publication
Date de publication:
01 11 2022
01 11 2022
Historique:
received:
26
05
2022
revised:
13
07
2022
accepted:
23
08
2022
pubmed:
12
10
2022
medline:
3
11
2022
entrez:
11
10
2022
Statut:
ppublish
Résumé
Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.
Identifiants
pubmed: 36219239
pii: 709803
doi: 10.1158/1940-6207.CAPR-22-0258
pmc: PMC9623234
mid: NIHMS1833862
doi:
Substances chimiques
RNA, Ribosomal, 16S
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
755-766Subventions
Organisme : NCI NIH HHS
ID : U54 CA221704
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA221705
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214005
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA264213
Pays : United States
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
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