» Articles » PMID: 39894787

Detection of an Intestinal Cell DNA Methylation Signature in Blood Samples from Neonates with Necrotizing Enterocolitis

Overview
Journal Epigenomics
Date 2025 Feb 2
PMID 39894787
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Necrotizing enterocolitis (NEC) is an often fatal intestinal injury that primarily affects preterm infants for which screening tools are lacking. We performed a pilot analysis of DNA methylation in peripheral blood samples from preterm infants with and without NEC to identify potential NEC biomarkers.

Methods: Peripheral blood samples were collected from infants at NEC diagnosis ( = 15) or from preterm controls ( = 13). Targeted genome-wide analysis was performed to identify DNA methylation differences between cases and controls.

Results: Broad differences between NEC cases and controls were identified in distinct genomic elements. Differences between surgical NEC cases and controls were frequently associated with inflammation. Deconvolution analysis to identify cell type-specific DNA signatures revealed increases in ileal, vascular endothelial, and cardiomyocyte cell type proportions and decreases in colonic and neuronal cell type proportions in blood from NEC cases relative to controls.

Conclusions: We identified marked differences in DNA methylation of peripheral blood samples from preterm infants with and without NEC. Increased ileal cell-specific methylation signatures in the blood of infants with NEC relative to controls, with a marked increase seen in surgical cases, provides rationale for further analysis of intestinal DNA methylation signatures as biomarkers of NEC.

References
1.
Good M, Chu T, Shaw P, McClain L, Chamberlain A, Castro C . Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis. Clin Epigenetics. 2020; 12(1):190. PMC: 7730811. DOI: 10.1186/s13148-020-00983-6. View

2.
Erger F, Norling D, Borchert D, Leenen E, Habbig S, Wiesener M . cfNOMe - A single assay for comprehensive epigenetic analyses of cell-free DNA. Genome Med. 2020; 12(1):54. PMC: 7315486. DOI: 10.1186/s13073-020-00750-5. View

3.
Leiva T, Lueschow S, Burge K, Devette C, McElroy S, Chaaban H . Biomarkers of necrotizing enterocolitis in the era of machine learning and omics. Semin Perinatol. 2023; 47(1):151693. PMC: 9975050. DOI: 10.1016/j.semperi.2022.151693. View

4.
Chiu R, Chan K, Gao Y, Lau V, Zheng W, Leung T . Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A. 2008; 105(51):20458-63. PMC: 2600580. DOI: 10.1073/pnas.0810641105. View

5.
Park Y, Figueroa M, Rozek L, Sartor M . MethylSig: a whole genome DNA methylation analysis pipeline. Bioinformatics. 2014; 30(17):2414-22. PMC: 4147891. DOI: 10.1093/bioinformatics/btu339. View