Ahnak and Nckap1l as potential diagnostic biomarkers and therapeutic targets in Landiolol-mediated sepsis treatment.

PURPOSE: Landiolol is a beta-blocker used in the treatment of Sepsis. However, how this drug influences key genes and pathways involved in disease remains unknown. This study aimed to explore potential biomarkers involved in the mechanism of Landiolol's action in sepsis.

METHODS

Two microarray datasets from the Gene Expression Omnibus database were downloaded. Differentially expressed genes (DEGs) were identified. Then, Landiolol-associated genes (lnd-DEGs) were screened using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis and protein-protein interaction (PPI) network investigation. Biomarkers were explored using three machine learning methods (LASSO, SVM-RFE, and RF), followed by diagnostic and prognostic analyses of these biomarkers.

RESULTS

After landiolol treatment, a total of 45 DEGs were identified when compared to normal samples. These genes were primarily associated with 357 biological functions, including the inositol phosphate metabolic process, and six key pathways, including the phosphatidylinositol signaling system. Using three different machine learning methods, 4 signature genes related to landiolol's action on sepsis were identified. Receiver operating characteristic (ROC) analysis demonstrated high predictive accuracy for Ahnak and Nckap1l in sepsis. Clinical correlation analysis revealed that Nckap1l and Ahnak were significantly associated with endotype and overall survival (OS) of sepsis, respectively. Finally, the prognostic value of Ahnak was validated through Kaplan-Meier analysis.

CONCLUSIONS

Ahnak and Nckap1l are potential diagnostic biomarkers and targets for therapeutic intervention in landiolol-induced sepsis following administration of Landiolol. Nckap1l can be used for endotype analysis of sepsis.