ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1662343
This article is part of the Research TopicExploring Molecular Mechanisms and Therapeutic Strategies for Inflammatory DiseasesView all articles
Clinical Association and Potential Molecular Mechanisms of Neonatal Sepsis and Necrotizing Enterocolitis
Provisionally accepted
- 1Children's Hospital of Soochow University, Suzhou, China
- 2Suzhou Medical College of Soochow University, Suzhou, China
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Background Necrotizing enterocolitis (NEC) is a severe intestinal disease affecting premature infants, with mortality rates of 20–30%. Neonatal sepsis (NS) is an independent risk factor for NEC; however, the shared molecular mechanisms and diagnostic biomarkers remain poorly understood. This study explores the molecular mechanisms linking NS and NEC and seeks potential diagnostic biomarkers. Methods We combined clinical cohort analysis with transcriptomics. Seventy-four NEC infants and 74 matched controls from Children's Hospital of Soochow University were analyzed to quantify the association between NS and NEC using logistic regression. Transcriptome data from NS (GSE25504) and NEC (GSE46619) were jointly analyzed to identify overlapping differentially expressed genes (DEGs) and construct a protein-protein interaction (PPI) network. Diagnostic efficacy of hub genes was tested in validation cohorts (GSE297483 and GSE69686). A transcription factor-mRNA regulatory network was also built using the TRRUST database. Results NS was associated with a significantly increased risk of NEC (OR = 3.02, P = 0.002). NEC infants showed higher systemic inflammatory markers and more frequent sepsis (60.81% vs 33.78%). Mechanistic studies identified 70 overlapping DEGs (69 upregulated, 1 downregulated), enriched in neutrophil chemotaxis and IL-17 signaling. FPR1, S100A12, and CSF3R emerged as potential biomarkers. External validation showed moderate diagnostic performance (AUC 0.723–0.813). Transcriptional regulation analysis implicated SPI1, NFKB1, and JUN as potential regulators. Conclusion NS may contribute to NEC development through shared inflammatory pathways involving FPR1, S100A12, and CSF3R. These genes showed diagnostic potential across both conditions and may mediate immune cell recruitment. While these findings suggest new directions for early identification in high-risk infants, further clinical validation is warranted to confirm therapeutic implications.
Keywords: Neonatal sepsis, necrotizing enterocolitis, Neutrophil chemotaxis, diagnostic biomarkers, Transcriptional regulatory network
Received: 09 Jul 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Liu, Sun, Bian, Li, Jin and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xueping Zhu, zhuxueping123456@outlook.com
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