miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls

Abstract

Background and Objectives. Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48–72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. Methods. This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Array. Results. A total of 11 very low birth-weight neonates with late-onset Gram-positive sepsis and 16 controls were analyzed. Further, 217 differentially expressed miRNAs were obtained between both groups. Subsequently, a combined analysis was performed with these miRNAs and 4297 differentially expressed genes. We identified 33 miRNAs that regulate our mRNAs, and the most relevant biological processes are associated with the immune system and the inflammatory response. Conclusions. The miRNA profiling in very low birth-weight neonates distinguishes late-onset Gram-positive sepsis versus control neonates.

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“…VEGFA was recognized as an important determinant of sepsis related morbidity and mortality in several early studies [25,26], therefore, it is not surprised that it is survival related. CCNA2 is reported as one of the connection genes generating positive effects during neonatal related sepsis [27], and was found to be correlated directly with the sequential organ failure (SOFA) score and mortality [28]. PRKDC mutation but not the mRNA level changes were reported in 2 studies describing the patient with sepsis presentations [29,30].…”

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