Identifying miR-431-5p as a promising candidate biomarker for early-onset severe preeclampsia through integrated bioinformatic and clinical analyses: a retrospective study.

BACKGROUND: Early-onset severe preeclampsia (EOSPE) is a serious pregnancy complication associated with 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 from placental tissue (GSE103542) and plasma (GSE234611), were screened to identify miRNAs consistently dysregulated in early-onset preeclampsia (EOPE) and to discover robust biomarker candidates. Weighted gene co-expression network analysis (WGCNA) was employed to identify key modules associated with preeclampsia (PE). The differentially expressed miRNAs (DEmiRNAs) were intersected with miRNAs from WGCNA-identified modules to prioritize candidates. 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 DEmiRNAs via reverse transcription quantitative polymerase chain reaction (RT-qPCR). The diagnostic value of these miRNAs was evaluated using receiver operating characteristic (ROC) curve analysis, and their correlations with clinical parameters were assessed.

RESULTS: Bioinformatics analysis identified miR-431-5p as a key molecule, with its expression was significantly upregulated in both serum and placental tissues of patients with EOSPE. Circulating miR-431-5p demonstrated promising diagnostic potential for EOSPE (AUC = 0.803). Its expression level positively correlated with systolic blood pressure (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). Conversely, it negatively correlated with gestational age at delivery (r = -0.562, P < 0.001) and neonatal birth weight (r = -0.503, P = 0.02). Multivariable regression analysis showed that after adjusting for confounding factors, miR-431-5p remained significantly positively associated with the occurrence of EOSPE. Animal experiments confirmed similar upregulation of miR-431-5p in the LPS-induced preeclampsia rat model.

CONCLUSIONS: In this study, miR-431-5p was significantly upregulated in EOSPE and demonstrated preliminary diagnostic potential. Its expression level was potentially associated with disease severity and adverse perinatal outcomes. These findings suggest that miR-431-5p may serve as a promising candidate biomarker for EOSPE.