Academic Journal
Multiomics analyses revealed the roles of the epithelial-mesenchymal transition and novel early candidate diagnostic biomarkers in neonatal necrotising enterocolitis.
| Τίτλος: | Multiomics analyses revealed the roles of the epithelial-mesenchymal transition and novel early candidate diagnostic biomarkers in neonatal necrotising enterocolitis. |
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| Συγγραφείς: | Liu XC; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Liu GB; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Department of General and Trauma Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China., Cheng C; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Zhu J; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, China.; Department of Pathology, Children's Hospital of Chongqing Medical University, Chongqing, China., Chen FF; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Ji Y; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Department of Laboratory, Children's Hospital of Chongqing Medical University, Chongqing, China., Zhang YN; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Yan XL; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Wang Q; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Li XY; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Ai Q; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., Shi Y; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China., He Y; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.; National Clinical Research Center for Children and Adolescents' Health and Diseases, Chongqing, China.; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.; Chongqing Municipal Health Commission Key Laboratory of Children's Vital Organ Development and Diseases, Chongqing, China. |
| Πηγή: | Clinical and translational medicine [Clin Transl Med] 2026 Sep; Vol. 16 (9), pp. e70793. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley Country of Publication: United States NLM ID: 101597971 Publication Model: Print Cited Medium: Internet ISSN: 2001-1326 (Electronic) Linking ISSN: 20011326 NLM ISO Abbreviation: Clin Transl Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : [Hoboken, NJ] : Wiley Original Publication: Heidelberg : Springer-Verlag |
| Ιατρικοί όροι (MeSH): | Enterocolitis, Necrotizing*/diagnosis , Enterocolitis, Necrotizing*/physiopathology , Biomarkers*/analysis , Biomarkers*/blood , Epithelial-Mesenchymal Transition*/physiology , Epithelial-Mesenchymal Transition*/genetics, Multiomics/methods ; Proteomics/methods ; Animals ; Mice ; Humans ; Infant, Newborn ; Disease Models, Animal ; Female |
| Περίληψη: | Background: Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease with incompletely understood pathogenesis and a lack of reliable early biomarkers. We investigated intestinal molecular alterations associated with NEC and explored candidate diagnostic biomarkers. Methods: Bulk proteomics of formalin-fixed paraffin-embedded intestinal tissues was integrated with spatial proteomics of an index NEC case, single-cell RNA sequencing, immunohistochemical validation, serum enzyme-linked immunosorbent assays, and a murine NEC model with pharmacological inhibition of Snail-mediated epithelial-mesenchymal transition (EMT). Results: Multiomics analyses indicated layer-associated epithelial injury, inflammatory activation, and EMT-like fibroblast/myofibroblast remodelling during NEC. Single-cell sequencing of six intestinal samples showed reduced epithelial-cell abundance with increased fibroblast and smooth-muscle-cell proportions in NEC. In the murine model, CYD19 treatment was associated with improved intestinal pathology, survival, inflammatory cytokine profiles, and barrier-related readouts. ANXA2, RPL13, RPL23A, and RPS28 were identified as tissue candidate biomarkers and validated by immunohistochemistry. Serum ANXA2 was higher in NEC than in available non-NEC controls (AUC, 0.944) and showed exploratory discrimination between medical NEC and highly suspected cow's-milk protein allergy; the adjusted AUC was 0.899. Conclusions: NEC is associated with inflammation-linked EMT-like intestinal remodelling and epithelial injury. ANXA2 and selected ribosomal proteins are candidate tissue biomarkers, while serum ANXA2 warrants prospective multicentre validation as a blood-based diagnostic and risk-stratification biomarker. Key Points: NEC was associated with epithelial injury, excessive inflammation, and EMT-like fibroblast/myofibroblast remodelling, as revealed by integrated bulk proteomics, spatial proteomics, and single-cell sequencing. Pharmacological inhibition of Snail-mediated EMT in a murine NEC model was associated with improved intestinal injury, inflammatory responses, barrier-related readouts, and survival. ANXA2, RPL13, RPL23A, and RPS28 were identified as candidate tissue biomarkers, while serum ANXA2 showed exploratory potential for NEC diagnosis and risk stratification. (© 2026 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.) |
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| Grant Information: | 2022YFC270480 National Key Research and Development Program of China; 82001602 National Natural Science Foundation of China; CHCMU-2024-XKDF-1002 Clinical Research Project for the Summit Program of Children's Hospital of Chongqing Medical University; CSTC2021jscx-gksb-N0015 Key Projects for Technological Innovation and Application Development of Chongqing; 2025QNXM057 Chongqing Science, Technology and Health Joint Project; CSTB2024NSCQ-MSX0491 Natural Science Foundation of Chongqing; 2022CQBSHTB3085 Special Funding for Postdoctoral Research Projects of Chongqing; 2023MD744152 China Postdoctoral Science Foundation; CYB240209 Chongqing Graduate Research Innovation Project; KJQN202600422 Chongqing Municipal Education Commission Science and Technology Research Project |
| Contributed Indexing: | Keywords: biomarkers; dysfunctions; epithelial–mesenchymal transition; neonatal necrotising enterocolitis; proteomics |
| Substance Nomenclature: | 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260916 Date Completed: 20260916 Latest Revision: 20260918 |
| Update Code: | 20260918 |
| PubMed Central ID: | PMC13578613 |
| DOI: | 10.1002/ctm2.70793 |
| PMID: | 42745358 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2001-1326 |
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| DOI: | 10.1002/ctm2.70793 |