Epigenetic changes associated with severe necrosis and survival in preterm infants with surgical necrotizing enterocolitis.

IF 3.1 3区医学 Q1 PEDIATRICS

Pediatric Research Pub Date : 2025-09-23 DOI:10.1038/s41390-025-04381-7

Nicole G Hall, Padma Garg, Jessica K Jackson, Neha Varshney, David Sawaya, Timothy D Howard, Parvesh Mohan Garg

{"title":"Epigenetic changes associated with severe necrosis and survival in preterm infants with surgical necrotizing enterocolitis.","authors":"Nicole G Hall, Padma Garg, Jessica K Jackson, Neha Varshney, David Sawaya, Timothy D Howard, Parvesh Mohan Garg","doi":"10.1038/s41390-025-04381-7","DOIUrl":null,"url":null,"abstract":"Background: We aim to determine the epigenetic changes assessed by DNA methylation associated with necrosis severity and survival in preterm infants with surgical necrotizing enterocolitis (NEC).Methods: Using Illumina's Infinium EPIC v2.0 BeadChips, the DNA methylation profiles of 46 infants with NEC were generated from intestinal tissue collected during laparotomy. Samples were categorized by disease severity and survival outcome. STRING functional enrichment analyses and MCODE network analyses of the genes found to contain CpG sites with significantly different methylation levels (Benjamini-Hochberg adjusted p-value ≤ 0.01) were used to investigate the biological relevance of the epigenetic differences between sample groups.Results: 4570 CpG sites showed a significant difference in methylation when comparing survivors (n = 34) and non-survivors (n = 12) of surgical NEC (p < 0.05). 19,518 CpG sites showed a significant difference in methylation when comparing NEC patients with low (n = 18) and high necrosis (n = 28) (p < 0.05). Genes with the greatest number of significant methylation sites include PRDM16, SEPTIN9, FOXP1, POLR1C, and several homeobox genes. NOTCH and Rap1 signaling were two of the major pathways identified.Conclusion: The DNA methylation profiles of infants with surgical NEC were found to differ, depending on necrosis severity and survival outcome.Impact: The DNA methylation profiles in surgical necrotizing enterocolitis (NEC) were found to differ depending on necrosis severity and survival outcome. Significant differences in the DNA methylation levels of thousands of genes helped identify molecular pathways that may be epigenetically regulated and involved in disease progression. These genes and molecular pathways are potential therapeutic targets for NEC, an incompletely understood and life-threatening disease.","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41390-025-04381-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: We aim to determine the epigenetic changes assessed by DNA methylation associated with necrosis severity and survival in preterm infants with surgical necrotizing enterocolitis (NEC).

Methods: Using Illumina's Infinium EPIC v2.0 BeadChips, the DNA methylation profiles of 46 infants with NEC were generated from intestinal tissue collected during laparotomy. Samples were categorized by disease severity and survival outcome. STRING functional enrichment analyses and MCODE network analyses of the genes found to contain CpG sites with significantly different methylation levels (Benjamini-Hochberg adjusted p-value ≤ 0.01) were used to investigate the biological relevance of the epigenetic differences between sample groups.

Results: 4570 CpG sites showed a significant difference in methylation when comparing survivors (n = 34) and non-survivors (n = 12) of surgical NEC (p < 0.05). 19,518 CpG sites showed a significant difference in methylation when comparing NEC patients with low (n = 18) and high necrosis (n = 28) (p < 0.05). Genes with the greatest number of significant methylation sites include PRDM16, SEPTIN9, FOXP1, POLR1C, and several homeobox genes. NOTCH and Rap1 signaling were two of the major pathways identified.

Conclusion: The DNA methylation profiles of infants with surgical NEC were found to differ, depending on necrosis severity and survival outcome.

Impact: The DNA methylation profiles in surgical necrotizing enterocolitis (NEC) were found to differ depending on necrosis severity and survival outcome. Significant differences in the DNA methylation levels of thousands of genes helped identify molecular pathways that may be epigenetically regulated and involved in disease progression. These genes and molecular pathways are potential therapeutic targets for NEC, an incompletely understood and life-threatening disease.

查看原文本刊更多论文

手术坏死性小肠结肠炎早产儿严重坏死和存活相关的表观遗传变化。

背景：我们的目的是通过DNA甲基化评估与外科坏死性小肠结肠炎（NEC）早产儿坏死严重程度和生存率相关的表观遗传变化。方法：使用Illumina公司的Infinium EPIC v2.0 BeadChips，从剖腹手术中收集的肠组织中生成46例NEC婴儿的DNA甲基化谱。样本按疾病严重程度和生存结果分类。利用STRING功能富集分析和MCODE网络分析发现含有甲基化水平显著不同的CpG位点的基因（Benjamini-Hochberg调整p值≤0.01）来研究样品组间表观遗传差异的生物学相关性。结果：4570个CpG位点的甲基化在比较手术性NEC幸存者（n = 34）和非幸存者（n = 12）时显示出显著差异(p结论：手术性NEC婴儿的DNA甲基化谱存在差异，这取决于坏死严重程度和生存结果。影响：发现手术坏死性小肠结肠炎（NEC）的DNA甲基化谱因坏死严重程度和生存结果而异。数千个基因DNA甲基化水平的显著差异有助于确定可能受表观遗传调控并参与疾病进展的分子途径。这些基因和分子途径是NEC的潜在治疗靶点，NEC是一种不完全了解且危及生命的疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pediatric Research 医学-小儿科

CiteScore

6.80

自引率

5.60%

发文量

473

审稿时长

3-8 weeks

期刊介绍： Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of children''s diseases and disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques relevant to developmental biology and medicine are acceptable, as are translational human studies