Placental Transcriptomic Analysis in Retinopathy of Prematurity Reactivation After Anti-VEGF Treatment.

Abstract

This study aimed to identify differentially expressed fetal factors in infants with reactivation of retinopathy of prematurity (ROP) using placental transcriptome analysis. This retrospective case series analyzed placental transcriptome differences between preterm infants with and without reactivation of ROP following anti-vascular endothelial growth factor (VEGF) treatment. We enrolled preterm infants who initially received 0.2 mg of ranibizumab for the treatment of ROP and whose maternal placentas were stored at Human Resources Bank. RNA sequencing was performed to identify differentially expressed genes (DEGs) between reactivated ROP (n = 4) and control (n = 8) groups. Bioinformatics analyses included functional enrichment, protein-protein interaction network construction, and hub gene identification. To evaluate predictive potential for ROP reactivation, genes with an ROC curve ≥ 0.7 were considered. A total of 329 DEGs were identified in the reactivated ROP group, comprising 207 upregulated and 122 downregulated genes. Among them, 15 hub genes, all upregulated, were related to VEGFA-VEGF receptor 2 signaling and trophoblast cell surface antigen 2 regulatory signaling. Of these, 9 hub genes (ACTG1, BSG, ETS1, FN1, FOXO4, IGFBP3, NUMB, MDM2, and SMARCA2) showed an AUC > 0.7, indicating high predictive potential. Except for FOXO4 and SMARCA2, the remaining 7 were associated with angiogenesis, including the VEGF pathway and endothelial cell activity. Upregulation of genes involved in the VEGFA-VEGF receptor 2 signaling pathway was significantly identified in the maternal placentas of infants with reactivated ROP. These 9 hub genes may serve as potential biomarkers for predicting ROP reactivation following anti-VEGF therapy.