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Identifying miR‑431‑5p as a biomarker for early‑onset severe preeclampsia through integrated bioinformatic and clinical analyses

bioinformatics
molecular-biology
gynecology-and-obstetrics

Abstract

Background. Early-onset severe preeclampsia (EOSPE) is a serious pregnancy complication leading to adverse maternal and neonatal outcomes. This study aimed to identify potential diagnostic biomarkers for EOSPE and to investigate their clinical significance.

Methods. MicroRNAs (miRNAs) expression datasets from the Gene Expression Omnibus（GEO）database—specifically, placental tissue (GSE103542) and plasma (GSE234611)—were screened to identify miRNAs that are consistently dysregulated in early-onset preeclampsia (EOPE). We aim to discover strong biomarker candidates. We employed Weighted Gene Co-expression Network Analysis（WGCNA）to identify key modules associated with preeclampsia (PE). Functional enrichment analysis predicted target genes and involved pathways. Clinical samples (serum and placental tissues from EOSPE patients and normal pregnant women) and a Lipopolysaccharide (LPS)-induced preeclampsia rat model were utilized to validate the expression of the differentially expressed miRNAs (DEmiRNAs) using Reverse Transcription Quantitative Polymerase Chain Reaction（RT-qPCR）. Its diagnostic value was evaluated by Receiver Operating Characteristic（ROC）curve analysis, and its correlation with clinical parameters was assessed.

Results. Bioinformatics analysis identified miR-431-5p as a key molecule, with its expression significantly upregulated in both serum and placental tissues of EOSPE patients. Circulating miR-431-5p shows promising diagnostic potential for EOSPE. Its expression level positively correlated with systolic（r =0.395，P=0.017）and diastolic blood pressure（r =0.41，P=0.013）, uric acid（r =0.389，P=0.02）, lactate dehydrogenase（r =0.399，P=0.018）, and the umbilical artery S/D ratio（r =0.457，P=0.01）, and negatively correlated with gestational age at delivery （r = -0.562，P＜0.001）and neonatal birth weight（r = -0.503，P=0.02）. Animal experiments confirmed similar upregulation of miR-431-5p in the LPS-induced preeclampsia rat model.

Conclusions. miR-431-5p is specifically highly expressed in EOSPE, possesses good diagnostic value, and its expression level correlates with disease severity, suggesting its potential as a novel molecular marker for the early diagnosis and assessment of EOSPE.

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