Identification and validation of a novel four-gene diagnostic model for neonatal early-onset sepsis with bacterial infection

Abstract

Neonatal early-onset sepsis (EOS) has unfortunately been the third leading cause of neonatal death worldwide. The current study is aimed at discovering reliable biomarkers for the diagnosis of neonatal EOS through transcriptomic analysis of publicly available datasets. Whole blood mRNA expression profiling of neonatal EOS patients in the GSE25504 dataset was downloaded and analyzed. The binomial LASSO model was constructed to select genes that most accurately predicted neonatal EOS. Then, ROC curves were generated to assess the performance of the predictive features in differentiating between neonatal EOS and normal infants. Finally, the miRNA-mRNA network was established to explore the potential biological mechanisms of genes within the model. Four genes (CST7, CD3G, CD247, and ANKRD22) were identified that most accurately predicted neonatal EOS and were subsequently used to construct a diagnostic model. ROC analysis revealed that this diagnostic model performed well in differentiating between neonatal EOS and normal infants in both the GSE25504 dataset and our clinical cohort. Finally, the miRNA-mRNA network consisting of the four genes and potential target miRNAs was constructed. Through bioinformatics analysis, a diagnostic four-gene model that can accurately distinguish neonatal EOS in newborns with bacterial infection was constructed, which can be used as an auxiliary test for diagnosing neonatal EOS with bacterial infection in the future.Conclusion: In the current study, we analyzed gene expression profiles of neonatal EOS patients from public databases to develop a genetic model for predicting sepsis, which could provide insight into early molecular changes and biological mechanisms of neonatal EOS.What is Known:• Infants with suspected EOS usually receive empiric antibiotic therapy directly after birth.• When blood cultures are negative after 48 to 72 hours, empirical antibiotic treatment is often halted. Needless to say, this is not a short time. Additionally, because of the concern for inadequate clinical sepsis production and the limited sensitivity of blood cultures, the duration of antibiotic therapy for the kid is typically extended.What is New:• We established a 4-gene diagnostic model of neonatal EOS with bacterial infection by bioinformatics analysis method. The model has better diagnostic performance compared with conventional inflammatory indicators such as CRP, Hb, NEU%, and PCT.