Zaikova Ekaterina K, Kaplina Aleksandra V, Petrova Natalia A, Pervunina Tatiana M, Golovkin Alexey S, Kostareva Anna A, Kalinina Olga V
Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia.
Research Laboratory of Physiology and Diseases of Newborns, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia.
World J Clin Pediatr. 2025 Sep 9;14(3):103652. doi: 10.5409/wjcp.v14.i3.103652.
Necrotizing enterocolitis (NEC) remains a prominent gastrointestinal emergency among infants, particularly term infants with congenital heart defects (CHD) being at high risk. The molecular processes that contribute to NEC have yet to be completely understood. The high mortality rates necessitate an active search for noninvasive biomarkers that can aid in the preclinical diagnosis and prognosis of NEC. MicroRNAs (miRs), which are involved in many biological processes in both health and disease, have been discovered to play an important role in regulating inflammation and immune responses via various signaling pathways.
To determine the plasma levels of miR-155, miR-221, miR-223, miR-320a, miR-451a as potential NEC biomarkers in term newborns with CHD.
This prospective cohort study included twenty-tree term newborns with CHD who underwent cardiac surgery on the median day of life (DOL) = 7. Nine of them developed NEC (Bell's stage IIA and IIIA) within 1 week of cardiac surgery (NEC newborns). Blood samples were collected before (median DOL = 5) and following (median DOL = 13) cardiac surgery. Levels of plasma miR-155-5p, miR-221-3p, miR-223-3p, miR-320a-3p, and miR-451a were determined using real-time polymerase chain reaction. The functional analysis was executed using the DIANA-miRPath v4.0.
Preoperatively, NEC newborns had significantly lower plasma levels of miR-155 (2.70-fold, = 0.020), miR-223 (2.42-fold, = 0.030), and miR-320a (3.62-fold, = 0.006) than newborns without NEC. Postoperatively, miR-451a levels differed significantly between the newborn groups, showing a 4.70-fold decrease ( = 0.014) in expression when clinical NEC symptoms appeared. According to receiver operating characteristic analysis, miR-320a was found to be the most effective predictive biomarker for NEC [area under the curve (AUC) = 0.835, 63% sensitivity, 100% specificity], while miR-451a was identified as a NEC biomarker (AUC = 0.835, 85.7% sensitivity, 76.9% specificity). Preoperatively, miR-155-5p, miR-223-3p, and miR-320a-3p were differentially expressed and targeted the forkhead box O and Hippo pathways ( < 0.01).
Our study demonstrates, for the first time, that plasma miR-320a-3p levels can be used as a preclinical biomarker for NEC in term newborns with CHD.
坏死性小肠结肠炎（NEC）仍是婴儿中一种突出的胃肠道急症，尤其是患有先天性心脏病（CHD）的足月儿风险很高。导致NEC的分子过程尚未完全了解。高死亡率促使人们积极寻找可辅助NEC临床前诊断和预后的非侵入性生物标志物。微小RNA（miR）参与健康和疾病中的许多生物学过程，已发现其通过各种信号通路在调节炎症和免疫反应中发挥重要作用。
确定miR-155、miR-221、miR-223、miR-320a、miR-451a的血浆水平作为患有CHD的足月儿潜在的NEC生物标志物。
这项前瞻性队列研究纳入了23名患有CHD的足月儿，他们在出生中位数日龄（DOL）=7时接受了心脏手术。其中9名在心脏手术后1周内发生了NEC（Bell IIA期和IIIA期）（NEC新生儿）。在心脏手术前（中位数DOL = 5）和术后（中位数DOL = 13）采集血样。使用实时聚合酶链反应测定血浆miR-155-5p、miR-221-3p、miR-223-3p、miR-320a-3p和miR-451a的水平。使用DIANA-miRPath v4.0进行功能分析。
术前，NEC新生儿的血浆miR-155（2.70倍，P = 0.020）、miR-223（2.42倍，P = 0.030）和miR-320a（3.62倍，P = 0.006）水平显著低于无NEC的新生儿。术后，miR-451a水平在新生儿组之间有显著差异，当出现临床NEC症状时，其表达下降了4.70倍（P = 0.014）。根据受试者工作特征分析，发现miR-320a是NEC最有效的预测生物标志物[曲线下面积（AUC）=
