Analysis of Differentially Expressed Genes and Molecular Pathways in Spontaneous Preterm Birth: A Bioinformatics Approach
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Abstract
Introduction: Preterm birth (PTB) accounts for 35% of neonatal mortality worldwide within 28 days of life. Limited understanding of its molecular mechanisms hampers the development of effective preventive strategies. Thus, this study aims to investigate dysregulated genes in the maternal blood and placenta of PTB women to unveil potential underlying mechanisms. Materials and Methods: A meta-analysis of differentially expressed genes (DEGs) in PTB was conducted using the limma R package and p-value combination method. Seven maternal blood and four placenta studies was chosen for this analysis. Accordingly, protein-protein interaction networks were constructed using STRING and visualised in Cytoscape. Network centrality was assessed using cytoHubba and CytoNCA tools in Cytoscape to rank key genes. MCODE was then used to identify highly interconnected gene clusters. Functional enrichment analysis was performed to obtain significant ontologies and pathways. Results: This study discovered 20 blood and 18 placenta hub genes, with IKBKG, HSP90AA1, and EGR1 being the most significantly enriched and central in maternal blood, and IGF1, FN1, and LOX genes for placenta. These DEGs mainly involve cytokine-mediated signalling pathways (maternal blood) and extracellular matrix organisation (placenta) biological pathways. Comparably, KEGG revealed them to be enriched in pathways of IL-17 signalling and ECM-receptor interaction, respectively. Conclusion: These DEGs have the potential to precisely identify PTB-risk individuals by revealing the underlying pathophysiology, allowing for more targeted and effective interventions. Notably, maternal blood DEGs are of particular interest, as they may serve as early, non-invasive biomarkers for PTB risk, enabling earlier detection and preventive care during pregnancy.
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