ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Computational-Experimental Strategy Identifies Co-Upregulated Biomarkers Linking Coronary Heart Disease and Type 2 Diabetes Pathogenesis
Provisionally accepted
- 1The First People's Hospital of Yunnan Province, Kunming, China
- 2First Affiliated Hospital of Kunming Medical University, Kunming, China
- 3Kunming University of Science and Technology School of Life Science and Technology, Kunming, China
- 4Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People's Hospital of Yunnan Province, 650032, ;, Kunming, China
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Background: 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. Methods: 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). Results: 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. Conclusion: 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.
Keywords: type 2 diabetes, coronary heart disease, diagnostic biomarkers, transcription factor, Bioinformatic technology
Received: 25 Jul 2025; Accepted: 30 Oct 2025.
Copyright: © 2025 Li, Cao, Yu, Che, He, Li, Jiang and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lijing Ma, drmalijing@163.com
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