Computational-experimental strategy identifies Co-upregulated biomarkers linking coronary heart disease and type 2 diabetes pathogenesis

TL;DR

This study identifies four biomarkers that are linked to both heart disease and type 2 diabetes, offering new diagnostic and therapeutic possibilities.

Contribution

The study introduces a novel computational-experimental approach to identify co-upregulated biomarkers shared between coronary heart disease and type 2 diabetes.

Findings

CPD, GGCT, SUZ12, and ZMYM2 are validated as shared diagnostic biomarkers for CHD and T2D.

These biomarkers show concurrent upregulation at both protein and mRNA levels in diseased vessels.

Aortic histopathology confirmed disease-specific changes in CHD and T2D mouse models.

Abstract

Coronary heart disease (CHD) and type 2 diabetes (T2D) represent a significant global comorbidity burden, with shared yet incompletely understood molecular mechanisms. This study aimed to identify shared diagnostic biomarkers and elucidate core pathways linking CHD and T2D pathogenesis.

Integrated bioinformatics of CHD/T2D transcriptomes identified shared differentially expressed genes (DEGs) and co-expression modules via Weighted Gene Co-expression Network Analysis (WGCNA). Receiver operating characteristic (ROC) analysis selected CPD, GGCT, SUZ12, and ZMYM2 as top diagnostic biomarkers. These predictions were validated using C57BL/6 and ApoE−/− mouse models of T2D/CHD. Aortic tissues underwent histopathology (Hematoxylin and Eosin (H&E), Oil Red O, Sirius Red) and multi-level molecular assays (immunofluorescence, Western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Bioinformatics revealed 328 shared DEGs, with CPD, GGCT, SUZ12, and ZMYM2 showing high diagnostic efficacy. T2D mice exhibited persistent hyperglycemia. Aortic histopathology confirmed disease-specific changes: atherosclerotic plaques in CHD and vascular basement membrane thickening in T2D. Critically, all four biomarkers showed concurrent upregulation in diseased vessels at both protein (immunofluorescence, Western blot) and mRNA (RT-qPCR) levels.

This study establishes CPD, GGCT, SUZ12, and ZMYM2 as shared CHD/T2D diagnostic biomarkers. Their validated co-upregulation highlights their dual-disease diagnostic and therapeutic potential.

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