OC17.08: Regulation of gene expression networks associated with placental dysfunction in late‐onset pre‐eclampsia

Pre-eclampsia is a heterogeneous disorder of pregnancy with two main subtypes, early and late-onset, suggesting potentially different underlying molecular mechanisms. Late-onset pre-eclampsia is more prevalent (70% of cases) and remains challenging to predict and manage. This study aimed to identify dysregulated genes, miRNAs and their interaction in term placentae from late-onset pre-eclampsia by utilising in silico analysis. Differential expressed genes (DEGs) and miRNAs (DEMs) were identified from subsets of public datasets GSE75010 (cases = 26, controls = 28) and GSE103542 (cases = 5, controls = 8) from Gene Expression Omnibus datasets. Differential expression and pathway analyses were performed using the R packages “limma” and “clusterProfiler”. A protein-protein interaction (PPI) network was generated via the STRING database. Target genes of DEMs were predicted with the R package “multiMiR”. DEGs that overlapped with the target genes of DEMs were defined as DEM-target DEGs for constructing a miRNA-mRNA network by Cytoscape software. We identified 216 DEGs (96 upregulated, 120 downregulated) and 20 DEMs (10 upregulated, 10 downregulated) with |logFC| > 2 and p < 0.05. The PPI network of 216 DEGs was constructed to select hub genes according to the Maximal Clique Centrality (MCC) score using CytoHubba in Cytoscape. The top ten genes with the highest MCC score were FN1, SEPRINE1, FLT1, TIMP3, ENG, EPAS1, PGF, LEP, SCARB1, and TIMP2. miRNA-mRNA regulatory networks implicated miR-548c-3p/u, miR-3065-5p, miR-3921, miR-34c-5p, and miR-3163 interaction with multiple DEGs. This study uncovered the top ten hub genes and ten DEG-related miRNAs associated with placental dysfunction in late-onset pre-eclampsia. In particular, miR-34-5p may play an important role in late-onset pre-eclampsia pathogenesis by regulating several hub genes such as SERPINE1, FLT1, LDHA, and ADAM12. These findings will be further validated in our local placental biobank (case = 26) to confirm their relevance in late-onset pre-eclampsia.