Abstract
BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most challenging chronic lung disease for prematurity, with difficulties in early identification. Given lncRNA emerging as a novel biomarker and the regulator of ferroptosis, this study aims to develop a BPD predictive model based on ferroptosis-related lncRNAs (FRLs). METHODS: Using a rat model, we firstly explored mRNA levels of ferroptosis-related genes and ferrous iron accumulation in BPD rat lungs. Subsequently, a microarray dataset of umbilical cord tissue from 20 preterm infants with BPD and 34 preterm infants without BPD were downloaded from the Gene Expression Omnibus databases. Random forest and LASSO regression were conducted to identify diagnostic FRLs. Nomogram was used to construct a predictive BPD model based on the FRLs. Finally, umbilical cord blood lymphocytes of preterm infants born before 32 weeks gestational age and term infants were collected and determined the expression level of diagnostic FRLs by RT-qPCR. RESULTS: Increased iron accumulation and several dysregulated ferroptosis-associated genes were found in BPD rat lung tissues, indicating that ferroptosis was participating in the development of BPD. By exploring the microarray dataset of preterm infants with BPD, 6 FRLs, namely LINC00348, POT1-AS1, LINC01103, TTTY8, PACRG-AS1, LINC00691, were determined as diagnostic FRLs for modeling. The area under the receiver operator characteristic curve of the model was 0.932, showing good discrimination of BPD. In accordance with our analysis of microarray dataset, the mRNA levels of FRLs were significantly upregulated in umbilical cord blood lymphocytes from preterm infants who had high risk of BPD. CONCLUSION: The incorporation of FRLs into a predictive model offers a non-invasive approach to show promise in improving early detection and management of this challenging chronic lung disease in premature infant, enabling timely intervention and personalized treatment strategies.