Immune checkpoints are a general term for a class of molecules that can regulate the body's immune function, and have a certain correlation with many diseases. However, immune checkpoints in sepsis are not well understood and potential immune checkpoint biomarkers need to be further developed. This study aims to study the effects of immune checkpoints on immune cells in patients with sepsis and identify biomarkers. We drew on the work of other scholars to get immune checkpoint genes from the published literature. Based on the GEO database, we identified differentially expressed immune checkpoint genes (DEICGs) in sepsis by differentially expressed gene (DEG) analysis. Then, CIBERSORT was applied to investigate the Infiltration level of 22 immune cells in the peripheral blood of sepsis, and we analyzed the correlation between DEICGs and the immune cells. After that, the weighted gene co-expression network (WGCNA) algorithm was used to explore new sepsis susceptibility modules, and the hub genes were extracted from the intersection of the results of WGCNA analysis and DEG. Subsequently, we performed Mendelian randomization (MR) analysis to explore the casual association of hub genes on sepsis. Positive results from MR analysis are considered the most reliable sepsis biomarkers and have been validated in external datasets by ROC analysis. A total of 36 DEICGs were identified by DEG. Through CIBERSORT, the correlation between the DEICGs and immune cells was investigated. Integrating the results of DEG and WGCNA, CD96, CD27, CD28, CD160, and TIGIT were identified as hub genes. In inverse variance weighting, we found that CD96 is a protective factor for sepsis with an OR of 0.952 (95%CI = 0.913 - 0.994, p = 0.027). According to ROC analysis, CD96 demonstrated excellent diagnostic efficacy, with an AUC of 0.945 (cutoff value = 4.074, 95%CI = 0.841 - 0.960). Generally, this research identified CD96 as a biomarker that could serve as a novel target for the diagnosis and therapy of sepsis.

Bo Chen, Quan Gong. WGCNA algorithm and Mendelian randomization analysis identified immune checkpoint CD96 as a biomarker for sepsis. International Journal of Frontiers in Medicine (2024), Vol. 6, Issue 9: 7-13. https://doi.org/10.25236/IJFM.2024.060902.

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