Identification of Potential Biomarkers for CAD Using Integrated Expression and Methylation Data

Area of Science:

• Genomics
• Epigenetics
• Cardiovascular Disease Research

Background:

• DNA methylation is crucial in coronary artery disease (CAD) pathogenesis by altering mRNA expression.
• Identifying methylation-regulated hub genes can yield novel CAD biomarkers.

Purpose of the Study:

• To identify and validate DNA methylation-regulated hub genes as potential biomarkers for CAD.
• To analyze gene expression and methylation datasets for CAD-specific molecular signatures.

Main Methods:

• Utilized Gene Expression Omnibus (GEO) datasets for gene expression and methylation analysis in peripheral blood leukocytes (PBLs).
• Employed computational approaches to identify regulatory networks and hub genes.
• Validated top candidate genes through differential expression and methylation analysis in a case-control study.

Main Results:

• Identified 535 differentially expressed-methylated genes (DEMGs), with enrichment in promoter regions (TSS200, 5'UTR).
• DEMGs are involved in histone methylation, post-transcriptional regulation, and RNA polymerase activity.
• Key pathways implicated include VEGF, adipocytokine, and PI3K-Akt signaling.
• Fibronectin 1 (FN1), PTEN, and POLR3A demonstrated differential expression and methylation, correlating with CAD status.

Conclusions:

• FN1, PTEN, and POLR3A are identified as potential diagnostic biomarkers for CAD in PBLs.
• DNA methylation patterns in PBLs offer insights into CAD pathogenesis and biomarker discovery.