Combined prediction of miR‐210 and miR‐374a for severity and prognosis of hypoxic–ischemic encephalopathy

Abstract

Background and AimHypoxic–ischemic encephalopathy (HIE) is a disorder featured by hypoxic and ischemic damages during the perinatal period and its high mortality (i.e., 15%–20%) could be partly attributed to late diagnosis. Therefore, miR‐210 and miR‐374a were investigated to find if they could improve the diagnostic values of S100B protein and neuron‐specific enolase (NSE) for HIE.MethodsAltogether 167 HIE newborns and 82 healthy newborns were recruited, and their blood were sampled for determining the levels of biomarkers. Specifically, S100B protein and NSE levels were detected based on the enzyme‐linked immunosorbent assay (ELISA) kit, while the expressions of miR‐210 and miR‐374a were quantified by quantitative reverse transcription–polymerase chain reaction (qRT‐PCR). Moreover, the receiver operating characteristic (ROC) curves were established to assess the diagnostic values of the above biomarkers for HIE. Finally, the correlation analysis between miR‐210/miR‐374 and Neonatal Behavioral Neurological Assessment (NBNA) scoring or Gesell intellectual development were also conducted.ResultsThe levels of miR‐210, miR‐374a, S100B protein, and NSE were significantly distinct between HIE patients and healthy newborns (p < .05). Besides, miR‐210 (r s = .573), miR‐374a (r s = .651), NSE level (r s = −.622), and S100B level (r s = −.55) were all, respectively, correlated with NBNA scoring with statistical significance (p < .05). Furthermore, it was revealed that the combined diagnosis of miR‐210, miR‐374a, S100B protein, and NSE could obtain the highest accuracy regarding pairs of mild HIE versus moderate HIE (AUC = 0.898), moderate HIE versus severe HIE (AUC = 0.922), mild HIE versus severe HIE (AUC = 0.996), and HIE versus control (AUC = 0.960). More than that, the four molecules were also remarkably associated with Gesell intellectual development (p < .05).ConclusionMiR‐210 and miR‐374a could help to elevate the diagnostic value and prognostic prediction of S100B protein and NSE for HIE.

Validation of Altered Umbilical Cord Blood MicroRNA Expression in Neonatal Hypoxic-Ischemic Encephalopathy

“…A piglet model reported temporal changes in expression after injury 39 and a 2017 clinical HIE study confirmed downregulation in umbilical cord blood in neonatal HIE. 40 This study also reported the downregulation of miR-181b in infants with moderate and severe HIE and compared the predictive ability of miR-181b with biochemical and clinical markers in HIE (Table 4). The strong NPV of 99% from miR-181b could make this miRNA a useful tool for the clinical setting because it is quantifiable and not subjective.…”

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

“…Therefore, finding new biomarkers to improve the diagnostic value of neuron‐specific enolase (NSE) and S100B protein is especially important. In 2017, Wang et al reported that the expressions of miR‐210 and miR‐374a, considered to be two important hypoxia‐associated miRNAs, were down‐regulated in blood samples of HIE newborns compared with those of healthy newborns. Joint analysis of miR‐210, miR‐374a, S100B protein and NSE help to elevate the diagnostic value and prognostic prediction for HIE by the ROC curves assay.…”

Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia

“…In this study, expression of rno-miR-190a-5p and rno-miR-374-5p in iliopsoas muscle was increased with decreasing body temperature. Previous reports suggest that the expression of both miRNAs fluctuates dynamically in response to hypoxia 24 , 25 . Hypothermic conditions induce tissue asphyxiation because blood is cooled by the inhalation of low-temperature air, and oxygen and hemoglobin do not dissociate in a cold environment.…”