Identification of Differentially Expressed Genes and Signaling Pathways in Placenta Tissue of Early-Onset and Late-Onset Pre-Eclamptic Pregnancies by Integrated Bioinformatics Analysis

BACKGROUND: Pre-eclampsia (PE) can be divided into 2 sub-groups: early-onset and late-onset PE. Although these sub-groups show overlapping molecular and cellular mechanisms and similar clinical manifestations, they are regarded as 2 different phenotypes with heterogeneous manifestations. The pathophysiological mechanisms underlying early-onset and late-onset PE still remain unclear. Therefore, the present study aimed to identify the key genes and pathways related to early-onset and late-onset PE, and to investigate the molecular mechanisms that are involved in gene regulation. MATERIAL/METHODS: Our analysis involved the Gene Expression Series (GSE) 74341 and GSE22526 from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus Database. These 2 microarray datasets included 15 patients with early-onset PE and 15 patients with late-onset PE. RESULTS: Our analyses identified 15 differentially expressed genes (DEGs), including CGA, EGR1, HBB, HBA2, LEP, and LHB. Gene Ontology (GO) functional annotation showed that the biological functions of these DEGs were mainly associated with steroid biosynthetic, oxidative stress, angiogenesis, and sex differentiation. Signaling pathway analyses showed that these DEGs were mainly involved in the prolactin signaling pathway, hormone metabolism, the AMPK signaling pathway, and the FoxO signaling pathway. Protein-protein interaction (PPI) network analysis identified 4 genes with the highest degree of interaction. The hub genes for this selection of DEGS were EGR1, LEP, and HBB. CONCLUSIONS: Integrated bioinformatic analyses provide us with a new approach to further understand the pathophysiology and molecular mechanisms underlying early-onset and late-onset PE. The DEGs identified in this study represent potential biomarkers for the early diagnosis of PE and may provide significant options the treatment of these 2 subtypes of PE.