Transcriptomic analysis reveals potential biomarkers for early-onset pre-eclampsia using integrative bioinformatics and LASSO based approach

Pre-eclampsia (PE) is a severe vascular disorder during pregnancy, significantly affecting maternal and fetal health worldwide. However, the exact molecular mechanism of its pathophysiology remains unclear, highlighting the need for reliable early diagnostic methods. Our primary aim of this study was to identify key genes (KGs) that may affect the outcome of patients with PE via integrated bioinformatics analysis. We analysed a gene expression dataset from the national center for biotechnology information (NCBI) sequence read archive (SRA) database and performed standard preprocessing steps, including quality assessment, trimming, genome alignment, and feature counts. Following this, normalization and differentially expressed genes (DEGs) were performed using Deseq2, which identified 781 DEGs were identified comprising 457 upregulated and 324 downregulated genes. Identified DEGs were significantly enriched in the cytokine interaction pathway and cellular calcium ion homeostasis. PPI network analysis revealed eight KGs (CXCL8, GAPDH, MMP9, SPP1, PTGS2, LEP, FGF7, and FGF10). These KGs were further found to be regulated by ten transcription factors (TFs), among which NF-kB1 and RELA consistently interact with all the KGs, and four microRNAs (miRNAs) such as hsa-mir-335-5p, has-mir-16a-5p, has-let-7b-5p, and has-mir-204-5p. The least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation (CV) confirmed all eight KGs may act as potential biomarkers based on their coefficients. Among these, GAPDH, SPP1, FGF7, and FGF10 emerged as novel biomarkers. Additionally, receiver operating characteristic (ROC) curve analysis for these novel biomarkers showed an area under the curve (AUC) of 0.869, demonstrating strong discriminatory power between the healthy and EOPE groups. The drug-gene interaction was performed by DrugMap database revealed an important interaction of GAPDH and FGF7 with FDA-approved drugs, indicating their therapeutic significance in PE. This analysis also facilitates drug repurposing for PE treatment.