Ferritinophagy-related prognostic genes UBE2Q1, NEDD4L, and TCP11L2 for prognosis prediction in sepsis.

Sepsis remains a critical global health threat characterized by high mortality and complex immune-metabolic dysregulation. This study identifies ferritinophagy-related prognostic genes (FRGs) that are causally linked to sepsis outcomes using a multi-omics approach integrating bulk and single-cell transcriptomics with Mendelian randomization. Among 1047 candidate genes, UBE2Q1, NEDD4L, and TCP11L2 were selected to build a risk model that effectively stratified sepsis patients and predicted mortality. Functional enrichment analysis revealed associations with oxidative phosphorylation, ribosome function, and Parkinson's disease pathways. Immune infiltration analysis identified increased γδ T and NK cell levels in high-risk patients, with significant correlations to prognostic genes. Single-cell RNA sequencing further revealed dynamic gene expression shifts across key immune cell types including T cells, monocytes, and platelets. Cell-cell communication and pseudo-time analyses highlighted the roles of UBE2Q1 and NEDD4L in immune regulation and development. This study provides preliminary clues that ferritin and autophagy-related genes may be involved in the pathogenesis of sepsis, and proposes potential molecular targets that can be used for prognostic evaluation and therapeutic intervention.