Identification and Validation of a Five-Gene Diagnostic Signature for Preeclampsia

Preeclampsia is the leading cause of morbidity and mortality for mothers and newborns worldwide. Despite extensive efforts made to understand the underlying pathology of preeclampsia, there is still no clinically useful effective tool for the early diagnosis of preeclampsia. In this study, we conducted a retrospectively multicenter discover-validation study to develop and validate a novel biomarker for preeclampsia diagnosis. We identified 38 differentially expressed genes (DEGs) involved in preeclampsia in a case-control study by analyzing expression profiles in the discovery cohort. We developed a 5-mRNA signature (termed PE5-signature) to diagnose preeclampsia from 38 DEGs using recursive feature elimination with a random forest supervised classification algorithm, including ENG, KRT80, CEBPA, RDH13 and WASH9P. The PE5-signature showed high accuracy in discriminating preeclampsia from controls with a receiver operating characteristic area under the curve value (AUC) of 0.971, a sensitivity of 0.842 and a specificity of 0.950. The PE5-signature was then validated in an independent case-control study and achieved a reliable and robust predictive performance with an AUC of 0.929, a sensitivity of 0.696, and a specificity of 0.946. In summary, we have developed and validated a five-mRNA biomarker panel as a risk assessment tool to assist in the detection of preeclampsia. This gene panel has potential clinical value for early preeclampsia diagnosis and may help us better understand the precise mechanisms involved.