Identification of Key Genes in Phosgene-induced Acute Lung Injury Using Bioinformatics Methods

Lina WangYuntao WangDaikun He^*

• Jinshan Hospital of Fudan University, Shanghai, China

Background: Phosgene is an industrially important but highly toxic gas that can cause severe respiratory injury upon accidental exposure, leading to acute lung injury (ALI). However, there are currently no effective therapeutic strategies to reverse phosgene-induced ALI (P-ALI). Identifying molecular biomarkers involved in P-ALI may provide a theoretical foundation for early diagnosis and targeted therapy. Objective: This study aimed to identify key genes and potential molecular mechanisms underlying P-ALI using integrative bioinformatics approaches, thereby supporting the development of novel diagnostic and therapeutic strategies. Methods: We analyzed transcriptomic data from rat lung tissues with P-ALI, combining our experimental dataset (Dataset 1) with two publicly available GEO datasets (GSE2411 and GSE17355; Datasets 2 and 3). Using a combination of differential expression analysis and weighted gene co-expression network analysis (WGCNA), we identified gene modules and hub genes associated with aspiration pneumonia (AP) and P-ALI. The diagnostic potential of candidate genes was evaluated through multivariate logistic regression and receiver operating characteristic (ROC) analysis. Results: Across the three datasets, we identified 1207, 4557, and 2290 differentially expressed genes (DEGs). WGCNA revealed three modules significantly correlated with AP: the deep in module (Dataset 1, 404 genes), dark gray module (Dataset 2, 2702 genes), and turquoise module (Dataset 3, 4327 genes). The intersection of DEGs and WGCNA module genes yielded four hub genes—GAB1, FASN, ENC1, and ENPP5—which were enriched in biological processes related to lipid biosynthesis, chemotaxis toward vascular endothelial growth factors, and neutrophil differentiation. A logistic regression model constructed using these four genes showed good diagnostic performance, as indicated by a high AUC value. Conclusion: The identified hub genes (GAB1, FASN, ENC1, and ENPP5) may serve as promising diagnostic biomarkers and potential therapeutic targets for phosgene-induced acute lung injury, providing a theoretical basis for precision medicine approaches in clinical practice.