ITGAV in PBMCs is identified as a hub gene in oxidative stress-related immunosuppression and delayed burn wound healing and is reversed by MnCl2
Peripheral blood mononuclear cell (PBMC) RNA-seq datasets from burn patients with sepsis were acquired from the Gene Expression Omnibus (GEO), and OSRGs were retrieved from the GeneCards database. Weighted gene coexpression network analysis (WGCNA) was performed to validate the relationships between burns and immune cells. Machine learning and logistic regression were employed to select hub genes, which were used to construct predictive signatures. High- and low-risk groups were defined by risk scores, and the expression of integrative hub genes was confirmed, with the results validated by real-time quantitative polymerase chain reaction (PCR) in PBMCs from 30 burn patients and burn models with different levels of severity. Integrin subunit alpha V (ITGAV) was confirmed as a hub gene, and its regulatory role was explored in vivo. Finally, the therapeutic role of MnCl2 was confirmed, and RNA-seq was performed to evaluate the associated signaling mechanisms. Overall design: Two OSRG molecular patterns exhibiting differential immune regulation were established. By WGCNA, the STRING database, and differential expression analysis, and a three-gene signature was selected by random forest (RF), least absolute shrinkage and selection operator (LASSO), and logistic regression, which included independent prognostic factors and performed well in receiver operating characteristic (ROC) and calibration curves. Finally, ITGAV was selected as an integrative hub gene, and the therapeutic role of MnCl2 in burn wound healing was determined to be associated with improved immunosuppression.