Downregulation of alcohol dehydrogenase family proteins suggests disrupted retinol metabolism in neonatal respiratory distress syndrome: an umbilical cord blood proteomics study

Why clinicians should know about it

• Picked for Biochemistry (medical) (top studies of the week, 18 October 2026): Alcohol dehydrogenase downregulation, neonatal proteomics

Abstract

OBJECTIVE: Neonatal respiratory distress syndrome (NRDS) is a prevalent complication in preterm infants, characterized by severe pulmonary dysfunction and elevated mortality rates. To systematically profile the umbilical cord blood proteome in neonates with NRDS, aiming to identify and explore their potential pathological mechanisms. METHODS: A case-control study was conducted, enrolling 60 preterm infants (< 34 weeks gestational) born between November 2024 and October 2025, including 32 NRDS cases and 28 matched controls. Umbilical cord blood plasma was analyzed via nanomaterial-based low-abundance protein enrichment (n_LAPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition mass spectrometry (DIA) mode. Differentially expressed proteins (DEPs) were identified using the Limma package. Bioinformatics analyses included Gene Ontology (GO), KEGG pathway enrichment, protein-protein interaction (PPI) network construction, and gene set enrichment analysis (GSEA). The Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest algorithm were employed to screen for core proteins and evaluate their discriminatory potential. RESULTS: A total of 7,529 high-confidence proteins were identified (5,090 passed quantification filters and entered differential expression analysis), with 157 DEPs between groups. These DEPs were significantly enriched in retinol metabolism, and complement and coagulation cascades. Both PPI network and GSEA analyses consistently highlighted the downregulation of alcohol dehydrogenase (ADH) family proteins (ADH1A, ADH1B, ADH4, ADH6) as the most prominent differential feature. An exploratory model based on five proteins, including ADH4, yielded AUCs of 0.982 (95% CI 0.95-1.00) and 0.838 (95% CI 0.63-1.00) in the training and test sets, respectively. CONCLUSION: The umbilical cord blood proteome of NRDS neonates is significantly disrupted, characterized by the downregulation of ADH family proteins. This suggests that ADH downregulation may contribute to NRDS pathogenesis by interfering with retinol metabolism, offering a novel mechanistic perspective. While the exploratory discriminatory model shows promise, it requires validation in large-scale prospective cohorts.

Abstract as published, via PubMed.