Evaluation of miRNAs in bacterial sepsis: comparison of circulating miRNAs and leukocyte miRNAs

This series contains serum-derived circulating miRNA profiles from patients with bacterial sepsis and trauma and healthy controls.Purpose: Aim: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate mRNA expression and play a critical role in development and infection control. Circulating miRNAs, found in the bloodstream, have attracted significant attention as potential biomarkers for malignancies and various other diseases. Our previous research suggested that circulating miRNAs may play a more prominent role in regulating the pathogenesis of bacterial sepsis. The aim of this study was to establish a validation cohort to confirm and strengthen these findings. Methods: Bacterial sepsis patients at Osaka University hospital were compared with healthy controls. RNA sequencing was performed on four sources: (1) leukocyte mRNA, (2) leukocyte miRNA, (3) circulating miRNA from derivation, and (4) circulating miRNA from validation. The cutoff values FDR <0.05, |log2 Fold Change| >1.5 were used. Results: The derivation cohort had 12 patients; the validation cohort had 17 patients and 4 healthy controls. (1)1,098 mRNAs in leukocytes (2)11 miRNAs in leukocytes (3) 323 circulating miRNAs (derivation)(4)343 circulating miRNAs (validation) were differentiated. Th2 signaling was suppressed, with GATA3 mRNA downregulated. 117 miRNAs related to GATA3 mRNA have been reported. Of these, 20 circulating miRNAs were identified in the derivation cohort, 17 varied in the validation cohort, and 14 were consistent across both cohorts. Conclusions: Circulating miRNAs may regulate bacterial sepsis better than leukocyte miRNAs. Fourteen circulating miRNAs could be biomarker candidates for bacterial sepsis.