Identification of Immune-Related Genes as Potential Biomarkers in Early Septic Shock.

Abstract

Introduction: Septic shock, a severe manifestation of infection-induced systemic immune response, poses a critical threat resulting in life-threatening multi-organ failure. Early diagnosis and intervention are imperative due to the potential for irreversible organ damage. However, specific and sensitive detection tools for the diagnosis of septic shock are still lacking.

Methods: Gene expression files of early septic shock were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT analysis was used to evaluate immune cell infiltration. Genes related to immunity and disease progression were identified using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis. CytoHubba was then employed to identify hub genes, and their relationships with immune cells were explored through correlation analysis. Blood samples from healthy controls and patients with early septic shock were collected to validate the expression of hub genes, and an external dataset was used to validate their diagnostic efficacy.

Results: Twelve immune cells showed significant infiltration differences in early septic shock compared to control, such as neutrophils, M0 macrophages, and natural killer cells. The identified immune and disease-related genes were mainly enriched in immune, cell signaling, and metabolism pathways. In addition, six hub genes were identified (PECAM1, F11R, ITGAL, ICAM3, HK3, and MCEMP1), all significantly associated with M0 macrophages and exhibiting an area under curve of over 0.7. These genes exhibited abnormal expression in patients with early septic shock. External datasets and real-time qPCR validation supported the robustness of these findings.

Conclusion: Six immune-related hub genes may be potential biomarkers for early septic shock.

Introduction: Septic shock, a severe manifestation of infection-induced systemic immune response, poses a critical threat resulting in life-threatening multi-organ failure. Early diagnosis and intervention are imperative due to the potential for irreversible organ damage. However, specific and sensitive detection tools for the diagnosis of septic shock are still lacking.

Methods: Gene expression files of early septic shock were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT analysis was used to evaluate immune cell infiltration. Genes related to immunity and disease progression were identified using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis. CytoHubba was then employed to identify hub genes, and their relationships with immune cells were explored through correlation analysis. Blood samples from healthy controls and patients with early septic shock were collected to validate the expression of hub genes, and an external dataset was used to validate their diagnostic efficacy.

Results: Twelve immune cells showed significant infiltration differences in early septic shock compared to control, such as neutrophils, M0 macrophages, and natural killer cells. The identified immune and disease-related genes were mainly enriched in immune, cell signaling, and metabolism pathways. In addition, six hub genes were identified (PECAM1, F11R, ITGAL, ICAM3, HK3, and MCEMP1), all significantly associated with M0 macrophages and exhibiting an area under curve of over 0.7. These genes exhibited abnormal expression in patients with early septic shock. External datasets and real-time qPCR validation supported the robustness of these findings.

Conclusion: Six immune-related hub genes may be potential biomarkers for early septic shock.