Abstract
ObjectivePreeclampsia is the main cause of maternal mortality due to a lack of diagnostic biomarkers and effective prevention and treatment. The immune system plays an important role in the occurrence and development of preeclampsia. This research aimed to identify significant immune-related genes to predict preeclampsia and possible prevention and control methods.MethodsDifferential expression analysis between normotensive and PE pregnancies was performed to identify significantly changed immune-related genes. Generalized linear model (GLM), random forest (RF), and support vector machine (SVM) models were established separately to screen the most suitable biomarkers for the diagnosis of PE among these significantly changed immune-related genes. The consensus clustering method was used to divide the PE cases into several subgroups to explore the function of the significantly changed immune-related genes in PE.ResultsThirteen significantly changed immune-related genes were obtained by the differential expression analysis. RF was the best model and was used to select the four most important explanatory variables (CRH, PI3, CCL18, and CCL2) to diagnose PE. A nomogram model was constructed to predict PE based on these four variables. The decision curve analysis (DCA) and clinical impact curves revealed that PE patients could significantly benefit from this nomogram. Consensus clustering analysis of the 13 differentially expressed immune-related genes (DIRGs) was used to identify 3 subgroups of PE pregnancies with different clinical outcomes and immune cell infiltration.ConclusionOur study identified four immune-related genes to predict PE and three subgroups of PE with different clinical outcomes and immune cell infiltration. Future studies on the three subgroups may provide direction for individualized treatment of PE patients.
Highlights
Preeclampsia (PE) is an idiopathic disease occurring during pregnancy, which can affect the function of multiple organs (Grandi et al, 2019; Phipps et al, 2019)
Both the heat map and the histogram showed that PI3, CCL18, CCL2, LTB, and CD48 were expressed at low levels in PE pregnancies compared to normotensive pregnancies
The expression levels of LEP, CGB1, CDF15, LHB, CGB8, CGA, CGB5, and corticotropin releasing hormone (CRH) were higher in the PE pregnancies than in the normotensive pregnancies
Summary
Preeclampsia (PE) is an idiopathic disease occurring during pregnancy, which can affect the function of multiple organs (Grandi et al, 2019; Phipps et al, 2019). Successful placental implantation depends on the precise regulation of the maternal immune system (Redman and Sargent, 2010; LaMarca et al, 2013). During this process, immune cells are needed for the invasive behavior observed in the decidual layer of the uterus. Immune cells are needed for the invasive behavior observed in the decidual layer of the uterus These immune cells gather around the trophoblasts and carry out different functions. An insufficient invasion of trophoblasts during placental implantation leads to defective placental spiral artery remodeling, and both placenta and fetus are in a relatively ischemic state (Lai et al, 2020)
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