Significance of m6A Regulators in the Diagnosis and Subtype Classification of Preeclampsia Using the Gene Expression Omnibus Database

Abstract Background: Preeclampsia(PE) is a common obstetric complication, it increases maternal and perinatal mortality. N6-methyladenosine (m6A) is the most common modification in eukaryotic mRNA, and this study aimed to investigate the role of m6A regulators in the diagnosis and subtype classification of PE.Methods: The mRNA profiles of GSE48424 and GSE75010 were downloaded from the Gene Expression Omnibus database. Differential expression analysis of m6A regulators was performed on the blood samples using the limma package of R, and significant results were obtained. A random forest model was used to predict PE. The expression of m6A regulators was also evaluated. Candidate genes were identified, and a nomogram was drawn. Principal component analysis was used to verify the classification of PE patients using a consensus clustering method based on m6A regulators found in serum samples. Infiltrating immune cells in blood samples were evaluated and quantified according to m6A scores. We compared the correlations of different m6A patterns with early-onset preeclampsia (EOPE) and severe preeclampsia (SPE).Results: We screened for the differential expression of three m6A regulators (YTHDF3, HNRNPA2B1, and CBLL1) in serum samples from women with PE and controls. In women with PE, the expression of YTHDF3 and HNRNPA2B1 in placenta and serum was significantly lower than in normal controls. PE can be predicted using a nomogram based on these two genes. Based on m6A regulators, GSE48424 PE patients can be separated into two subgroups (Clusters A and B). Seven immune cell subtypes showed varying degrees of infiltration. Higher m6A scores were found in Cluster A than in Cluster B. PE patients in Cluster B were more likely to have SPE. EOPE and SPE were more likely to occur in PE patients in Cluster A with high m6A scores. Women with SPE or EOPE exhibit high levels of YTHDF3.Conclusions: This study shows that m6A regulators are differentially expressed in serum samples from PE patients and that they have potential diagnostic and typing value. Further research on PE subgroups may lead to more precise prevention and treatment methods.