Lysosome-related biomarkers in peripheral blood immune cells discriminate sepsis from SIRS

This study aimed to screen lysosome-related genes that distinguish sepsis from Systemic Inflammatory Response Syndrome (SIRS), in order to provide potential targets for the differential diagnosis of sepsis and for lysosome-targeted therapeutic strategies. Peripheral blood samples were collected from 12 SIRS patients and 20 sepsis patients for RNA sequencing and differential expression analysis. Meanwhile, lysosome-related gene sets were obtained from the Gene Ontology database. The intersection was taken between the differentially expressed genes and the lysosomal gene sets. Subsequently, Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on these overlapping genes. Meta-analysis was used to screen for core genes, and their diagnostic efficacy was evaluated using Receiver Operating Characteristic (ROC) curves. Furthermore, single-cell RNA sequencing was performed to identify the immune cell types that predominantly express the core genes, facilitating the selection of appropriate cell models for subsequent experimental validation. Functional enrichment analysis revealed that these 21 overlapping genes were significantly enriched in biological pathways such as receptor metabolic process, autophagy, vacuolar transport, cellular catabolic process, and lysosomal transport. Meta-analysis identified four core genes: CD1C, RNASE6, and SNCA were significantly downregulated in the sepsis group, while DRAM1 was significantly upregulated. Diagnostic efficacy evaluation demonstrated that all four core genes possessed good discriminatory value, with AUC as follows: CD1C (0.758), DRAM1 (0.888), RNASE6 (0.737), and SNCA (0.765). Single-cell RNA sequencing analysis suggested that CD1C and RNASE6 are primarily expressed in circulating monocyte-macrophages and B cells, DRAM1 is mainly expressed in circulating monocyte-macrophages, and SNCA is predominantly expressed in circulating monocyte-macrophages and platelets. The four core genes identified in this study could serve as potential diagnostic biomarkers to distinguish sepsis from SIRS. Their expression is mainly enriched in circulating monocyte-macrophages in peripheral blood, providing new directions for future research.