Liu Chan, Ai Qing, Yang Jingli, Fan Ying, Jia Wen, Si Leyu, Yao Yuting, Chen Feifan, Liu Shiyue, He Yu, Shi Yuan
Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China.
iScience. 2025 Jun 25;28(8):113007. doi: 10.1016/j.isci.2025.113007. eCollection 2025 Aug 15.
Neonatal acute respiratory distress syndrome (NARDS) is challenging to differentiate from other respiratory conditions, and gestational age (GA) may influence gene expression. This study characterized whole blood transcriptomic profiles of NARDS in a pilot cohort of 48 neonates with respiratory distress, demonstrating a significant GA-dependent modulation of gene expression. Functional analyses revealed prominent involvement of interferon-related pathways in NARDS, with greater suppression in neonates born before 34 weeks. Immune cell infiltration was observed in term or late preterm neonates but was absent in more preterm cases. Machine learning identified three key predictive genes, among which and were validated in an independent cohort, with area under the curve ranging from 0.68 to 0.83 across different GAs. The gene changes were also confirmed in a neonatal lipopolysaccharide-induced lung injury mouse model. These findings highlight the potential predictive and therapeutic value of and for NARDS.
新生儿急性呼吸窘迫综合征（NARDS）与其他呼吸系统疾病的鉴别具有挑战性，且胎龄（GA）可能会影响基因表达。本研究对48例有呼吸窘迫的新生儿组成的试验队列中的NARDS全血转录组谱进行了特征分析，结果表明基因表达存在显著的GA依赖性调节。功能分析显示干扰素相关通路在NARDS中显著参与，在34周前出生的新生儿中抑制作用更强。足月儿或晚期早产儿中观察到免疫细胞浸润，但在更早出生的病例中未观察到。机器学习确定了三个关键预测基因，其中 和 在一个独立队列中得到验证，在不同GA下曲线下面积范围为0.68至0.83。在新生儿脂多糖诱导的肺损伤小鼠模型中也证实了基因变化。这些发现突出了 和 对NARDS的潜在预测和治疗价值。
