AUTHOR=Zhang Yanpeng , Sun Jingyang , Lin Yihan , Jiang Rongxuan , Dong Niuniu , Dong Huanhuan , Li Peng , Feng Jinteng , Zhu Zijiang , Zhang Guangjian 

TITLE=Machine learning-based prediction model for lung ischemia-reperfusion injury: insights from disulfidptosis-related genes

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1545111

DOI=10.3389/fphar.2025.1545111

ISSN=1663-9812

ABSTRACT=ObjectiveThis study aims to explore potential ischemia-reperfusion injury (IRI) predictive biomarkers related to disulfidptosis following lung transplantation.MethodsThe study utilized datasets from the GEO database, specifically GSE145989 and GSE127003, which include samples of lung cold ischemia and reperfusion following transplantation. Differential expressed analysis and functional enrichment analysis were conducted to identify key genes associated with lung transplant IRI. Multiple machine learning algorithms (Generalized Linear Model, Support Vector Machine, and Random Forest) were applied for joint screening, leading to the construction of a predictive model. The CIBERSORT method was used to assess the infiltration levels of immune cells in lung tissue samples post-transplant. Finally, cell line and animal experiments were carried out to validate the effectiveness and applicability of the model.ResultsA total of 14,592 hub differential-expressed genes were identified, showing significant changes in cold ischemia and reperfusion samples. Using the three machine learning algorithms for joint analysis, a predictive model composed of SLC7A11 and LRPPRC was constructed. This model demonstrated excellent predictive efficacy across multiple datasets, with area under the curve (AUC) values of 0.742 and 0.938, respectively. Additionally, significant differences in neutrophils and macrophages were observed in lung transplant cold ischemia and reperfusion samples. Based on the differential genes associated with disulfidptosis and utilizing the CMap database, we identified two potential drugs targeting IRI: olanzapine and vortioxetine. Ultimately, cell line and animal experiments validated the predictive model’s reliability and potential clinical value, revealing that disulfidptosis presents in IRI, and high SLC7A11 expression promotes IRI, while low LRPPRC expression contributes to its occurrence.ConclusionSLC7A11 and LRPPRC can serve as predictive biomarkers for IRI following lung transplantation.