A cuproptosis-related gene signature and the protective role of CDKN1A in sepsis-induced acute respiratory distress syndrome
Abstract
BackgroundSepsis-induced acute respiratory distress syndrome (ARDS) is associated with high mortality, and reliable molecular biomarkers remain limited. This study aimed to identify candidate cuproptosis-related diagnostic biomarkers and investigate the protective role of CDKN1A.MethodsDifferentially expressed genes from GSE10474 were intersected with cuproptosis-related genes, followed by functional enrichment, protein–protein interaction analysis, and machine learning using LASSO, random forest, and support vector machine algorithms. The resulting signature was evaluated in GSE32707 and GSE66890. Immune infiltration and single-cell transcriptomic analyses were performed, followed by experimental evaluation of CDKN1A overexpression in LPS-stimulated alveolar epithelial cells.ResultsAn eight-gene signature comprising CDKN1A, MNDA, TREM1, ACP6, APOO, CHPT1, PIAS3, and SNRNP35 was identified. The models achieved AUCs of 0.786–0.886 in the training cohort and 0.654–0.745 in the validation cohorts. Immune analyses revealed dataset-dependent alterations in immune cell populations. CDKN1A overexpression attenuated LPS-induced cytotoxicity, improved cell viability and tight junction protein expression, modulated cuproptosis-related markers, reduced intracellular copper and mitochondrial reactive oxygen species, and preserved mitochondrial membrane potential.ConclusionThe eight-gene signature represents a candidate diagnostic tool for sepsis-induced ARDS. CDKN1A overexpression is associated with protection against LPS-induced alveolar epithelial injury and modulation of cuproptosis-related and mitochondrial markers. Further mechanistic and prospective clinical validation is required.
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BibTeX
@article{liu2026cuproptosisrelated,
title = {{A cuproptosis-related gene signature and the protective role of CDKN1A in sepsis-induced acute respiratory distress syndrome}},
author = {Yue Liu and Ni Wang and Wei Chang and Jingyuan Xu and Fengmei Guo},
journal = {Frontiers in Molecular Biosciences},
year = {2026},
month = nov,
doi = {10.3389/fmolb.2026.1962671},
url = {https://www.frontiersin.org/articles/10.3389/fmolb.2026.1962671},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A cuproptosis-related gene signature and the protective role of CDKN1A in sepsis-induced acute respiratory distress syndrome
AU - Yue Liu
AU - Ni Wang
AU - Wei Chang
AU - Jingyuan Xu
AU - Fengmei Guo
PY - 2026
DA - 2026/11/02
JO - Frontiers in Molecular Biosciences
DO - 10.3389/fmolb.2026.1962671
UR - https://www.frontiersin.org/articles/10.3389/fmolb.2026.1962671
AB - BackgroundSepsis-induced acute respiratory distress syndrome (ARDS) is associated with high mortality, and reliable molecular biomarkers remain limited. This study aimed to identify candidate cuproptosis-related diagnostic biomarkers and investigate the protective role of CDKN1A.MethodsDifferentially expressed genes from GSE10474 were intersected with cuproptosis-related genes, followed by functional enrichment, protein–protein interaction analysis, and machine learning using LASSO, random forest, and support vector machine algorithms. The resulting signature was evaluated in GSE32707 and GSE66890. Immune infiltration and single-cell transcriptomic analyses were performed, followed by experimental evaluation of CDKN1A overexpression in LPS-stimulated alveolar epithelial cells.ResultsAn eight-gene signature comprising CDKN1A, MNDA, TREM1, ACP6, APOO, CHPT1, PIAS3, and SNRNP35 was identified. The models achieved AUCs of 0.786–0.886 in the training cohort and 0.654–0.745 in the validation cohorts. Immune analyses revealed dataset-dependent alterations in immune cell populations. CDKN1A overexpression attenuated LPS-induced cytotoxicity, improved cell viability and tight junction protein expression, modulated cuproptosis-related markers, reduced intracellular copper and mitochondrial reactive oxygen species, and preserved mitochondrial membrane potential.ConclusionThe eight-gene signature represents a candidate diagnostic tool for sepsis-induced ARDS. CDKN1A overexpression is associated with protection against LPS-induced alveolar epithelial injury and modulation of cuproptosis-related and mitochondrial markers. Further mechanistic and prospective clinical validation is required.
SN - 2296-889X
ER -