Abstract
PURPOSE: Screening of lysosome-related genes in sepsis patients to provide direction for lysosome-targeted therapy. METHODS: Peripheral blood samples were obtained from 22 patients diagnosed with sepsis and 10 normal controls for the purpose of RNA sequencing and subsequent analysis of differential gene expression. Concurrently, lysosome-related genes were acquired from the Gene Ontology database. The intersecting genes between the differential genes and lysosome-related genes were then subjected to PPI, GO and KEGG analyses. Core genes were identified through survival analysis, and their expression trends in different groups were determined using meta-analysis. Single-cell RNA sequencing was used to clarify the cellular localization of core genes. RESULTS: The intersection of 1328 sepsis-differential genes with 878 lysosome-related genes yielded 76 genes. PPI analysis showed that intersecting genes were mainly involved in Cellular process, Response to stimulus, Immune system process, Signal transduction, Lysosome. GO and KEGG analysis showed that intersecting genes were mainly involved in leukocyte mediated immunity, cell activation involved in immune response, lytic vacuole, lysosome. Survival analysis screened four genes positively correlated with sepsis prognosis, namely GNLY, GZMB, PRF1 and RASGRP1. The meta-analysis revealed that the expression levels of these four genes were significantly higher in the normal control group compared to the sepsis group, which aligns with the findings from RNA sequencing data. Furthermore, single-cell RNA sequencing demonstrated that T cells and NK cells exhibited high expression levels of GNLY, GZMB, PRF1, and RASGRP1. CONCLUSION: GNLY, GZMB, PRF1, and RASGRP1, which are lysosome-related genes, are closely linked to the prognosis of sepsis and could potentially serve as novel research targets for sepsis, offering valuable insights for the development of lysosome-targeted therapy. The clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019.