Transcriptomic analysis reveals potential biomarkers for early-onset pre-eclampsia using integrative bioinformatics...

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Pre-eclampsia (PE) is a severe pregnancy disorder with unclear molecular mechanisms.
• Early diagnosis and effective treatments for PE are urgently needed.
• Identifying key genes (KGs) is crucial for understanding PE pathophysiology.

Purpose of the Study:

• To identify key genes (KGs) associated with pre-eclampsia (PE) outcomes using integrated bioinformatics analysis.
• To discover novel biomarkers for early PE diagnosis.
• To explore therapeutic targets and drug repurposing opportunities for PE.

Main Methods:

• Analysis of gene expression datasets from NCBI SRA database.
• Preprocessing, normalization, and differential gene expression analysis using Deseq2.
• Protein-protein interaction (PPI) network construction, transcription factor (TF) and microRNA (miRNA) regulatory network analysis.
• LASSO regression and ROC curve analysis for biomarker validation.
• Drug-gene interaction analysis using DrugMap.

Main Results:

• Identified 781 differentially expressed genes (DEGs) in PE, enriched in cytokine interaction and calcium homeostasis pathways.
• Eight key genes (KGs) were identified: CXCL8, GAPDH, MMP9, SPP1, PTGS2, LEP, FGF7, and FGF10.
• NF-kB1 and RELA were identified as key transcription factors, and four miRNAs (hsa-mir-335-5p, has-mir-16a-5p, has-let-7b-5p, has-mir-204-5p) were regulators.
• GAPDH, SPP1, FGF7, and FGF10 emerged as novel PE biomarkers with strong discriminatory power (AUC=0.869).
• GAPDH and FGF7 showed significant interactions with FDA-approved drugs, suggesting therapeutic potential.

Conclusions:

• Integrated bioinformatics analysis successfully identified novel key genes and potential biomarkers for pre-eclampsia.
• The identified biomarkers, particularly GAPDH, SPP1, FGF7, and FGF10, demonstrate significant diagnostic potential for PE.
• The study highlights therapeutic significance and facilitates drug repurposing for PE by revealing drug-gene interactions.