Sepsis is an inflammation-induced organ dysfunction, and its pathogenesis includes immune regulation disorders, inflammatory responses, and coagulation disorders. According to statistics, approximately 48.9 million people worldwide suffer from sepsis, of which 11 million die, accounting for 1/5 of the total number of deaths in the world. Although diagnosis and treatment methods, such as mechanical ventilation, fluid therapy and sepsis warning scores have improved continuously, and the morbidity and mortality of sepsis have decreased, they are still the main cause of death in critically ill patients. A cross-sectional survey showed that the incidence of sepsis in intensive care unit (ICU) patients in China was approximately 20%, and the 90-day mortality rate was 35.5%. The fatality rate of the virus remains high. This may be due to the lack of biomarkers for the detection of early sepsis and effective treatment of sepsis . Therefore, understanding the molecular mechanisms of sepsis is necessary for the majority of medical workers to find methods for treating and diagnosing sepsis. In this study, 292 differentially expressed genes were screened out by analysing the self-test data, including 128 upregulated genes and 164 downregulated genes. The GSE131761 dataset screened 294 differentially expressed genes, including 130 upregulated genes and 164 downregulated genes. Then, the differentially expressed genes in the two datasets were intersected, and a total of 9 intersecting genes were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these genes to determine the gene function and the associated signalling pathways. Finally, 5 main central genes were identified, including SIGLEC10, VSTM1, GYPB, OPTN, and GIMAP7, and the main enrichment pathways of the 5 differentially expressed genes were KEGG_PANTOTHENATE_AND_COA_BIOSYNTHESIS and KEGG_FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS. The VSTM1 enrichment pathway was KEGG_STARCH_AND_SUCROSE_METABOLISM and KEGG_STEROID_ path. GYPB-enriched pathways were KEGG_OLFACTORY_TRANSDUCTION, KEGG_LINOLEIC_ACID_METABOLISM; OPTN-enriched pathways were KEGG_OLFACTORY_TRANSDUCTION, KEGG_LINOLEIC_ACID_METABOLISM; GIMAP7-enriched pathways were KEGG_TASTE_TRANSDUCTION, KEGG_BUTANOATE_METABOLISM.
Australian scholars have found that most sialic acid-binding immunoglobulin-like lectins (SIGLECs) suppress immune cell function but are expressed at lower levels on human T cells. Soluble CD52 inhibits T-cell signalling by ligating Siglec-10. We examined Siglec-10 expression at the RNA and protein levels in human CD4(+) T cells. These results were consistent with the homeostatic role of Siglec-10 in human CD4(+) T cells . VSTM1 (V-set and 1-containing transmembrane domain) is a novel membrane molecule identified from immunomics, and it has two major isoforms, VSTM1-v1 and VSTM1-v2. VSTM1-v1 is a type I transmembrane protein, and VSTM1-v2 is a typical secreted protein. Compared with VSTM1-v1, it only lacks the transmembrane domain . Some scholars have used whole blood eQTL data from Chinese populations. The identification of SNPs that regulate the expression of the gene encoding SIRL-1, VSTM1, underscores the role of cellular subsets and this inhibitory immune receptor in maintaining skin immune homeostasis . The GYPB gene is mainly studied in immunohaematology research, blood group genomics, etc. , OPTN (optineurin) is a macroautophagy/autophagy (hereafter referred to as autophagy) receptor that plays a key role in selective autophagy, which combines autophagy with bone metabolism . GIMAP7 is closely related to the immune process of tumours . Related core genes may affect the immune function of patients with sepsis by upregulating or downregulating their expression, which further affects the development and prognosis of sepsis. For example, the Siglec family is a transmembrane receptor expressed on the surface of immune cells and plays a role in infectious diseases. Regulating the role of immune balance, Siglec-9 regulates the polarization phenomenon of macrophages through the endocytosis of Toll-like receptor 4 (TLR4), which in turn inhibits the action of neutrophils. Siglec-10 inhibits risk-associated molecular patterns (DAMPs), helps T cells to initiate antigen-antibody responses, and reduces the number of B cells to attenuate the inflammatory response .
Subsequently, LASSO model expression difference analysis, WGCNA, immune infiltration analysis, GSEA, and key gene regulatory network analysis were performed on these five genes, which were good predictors of disease. Immune infiltration in the sepsis group, according to the ROC curve of diagnostic efficacy validation, indicated that the higher the AUC value, the better the prediction performance. The results showed that the AUC values of the five core genes were GIMAP7-AUC: 0.780 (0.702–0.859), GYPB-AUC: 0.647 (0.546–0.748), OPTN-AUC: 0.706 (0.612–0.800), SIGLEC10-AUC: 0.772 (0.685–0.859), and VSTM1-AUC: 0.762 (0.682–0.842). It is suggested that the five core genes can better predict the occurrence and development of the disease; the above five genes have good diagnostic value in septic shock patients. In conclusion, this study identified DEGs that may be associated with septic shock using bioinformatics research methods. These five genes may serve as potential targets for sepsis diagnosis and treatment, thus providing a scientific basis for the study of the molecular mechanism of sepsis.