Establishment and validation of a predictive model of preeclampsia based on transcriptional signatures of 43 genes in decidua basalis and peripheral blood

基于蜕膜基底层和外周血中43个基因的转录特征,建立并验证先兆子痫预测模型

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Abstract

Preeclampsia (PE) has an increasing incidence worldwide, and there is no gold standard for prediction. Recent progress has shown that abnormal decidualization and impaired vascular remodeling are essential to PE pathogenesis. Therefore, it is of great significance to analyze the decidua basalis and blood changes of PE to explore new methods. Here, we performed weighted gene co-expression network analysis based on 9553 differentially expressed genes of decidua basalis data (GSE60438 includes 25 cases of PE and 23 non-cases) from Gene Expression Omnibus to screen relevant module-eigengenes (MEs). Among them, MEblue and MEgrey are the most correlated with PE, which contains 371 core genes. Subsequently, we applied the logistic least absolute shrinkage and selection operator regression, screened 43 genes most relevant to prediction from the intersections of the 371 genes and training set (GSE48424 includes 18 cases of PE and 18 non-cases) genes, and built a predictive model. The specificity and sensitivity are illustrated by receiver operating characteristic curves, and the stability was verified by two validation sets (GSE86200 includes 12 cases of PE and 48 non-cases, and GSE85307 includes 47 cases of PE and 110 non-cases). The results demonstrated that our predictive model shows good predictions, with an area under the curve of 0.991 for the training set, 0.874 and 0.986 for the validation sets. Finally, we found the 43 key marker genes in the model are closely associated with the clinically accepted predictive molecules, including FLT1, PIGF, ENG and VEGF. Therefore, this predictive model provides a potential approach for PE diagnosis and treatment.

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