Fcer1g and St3gal1: Macrophage-associated angiogenesis biomarkers and therapeutic targets in sepsis-induced acute lung injury

Background: Acute lung injury (ALI) involves the release of growth factors and inflammatory mediators from damaged pulmonary tissues, fostering endothelial cell proliferation, migration, and vascular lumen formation, thereby driving pathological angiogenesis. Macrophages contribute to angiogenesis and vascular homeostasis, but their dysregulation in pathological states worsens vascular dysfunction. This study aims to identify macrophage-associated angiogenesis-related genes as novel diagnostic biomarkers and therapeutic targets for sepsis-associated ALI (SALI). Methods: Transcriptomic datasets from the GEO database were analyzed using differential expression profiling and weighted gene co-expression network analysis (WGCNA) to identify candidate genes. These candidates were compared with macrophage- and angiogenesis-related gene sets from GENECARDS for functional prioritization. Three machine learning algorithms (LASSO regression, random forest, and SVM) were employed to refine predictive biomarkers, followed by immune infiltration analysis (via CIBERSORT) to assess correlations with immune subsets. Single-cell RNA sequencing and RT-PCR were used for spatial validation of gene expression. Results: Two macrophage-associated angiogenesis-related genes, Fcer1g (FCER1G) and St3gal1 (ST3GAL1), were identified as key biomarkers. Both genes showed significant upregulation in the training cohort (p 0.85). Immune correlation analysis indicated strong positive associations with macrophage infiltration (p 2.0, p