Integrated bioinformatics analysis and mouse validation identify C7 and MFAP4 as candidate genes associated with type 2 diabetes and atherosclerosis
- 1Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, No.295 Xichang Rd, Kunming, Yunnan 650032 China
- 2Department of Cardiology, 920th Hospital of Joint Logistics Support Force of the Chinese People’s Liberation Army, No.212 Daguan Rd, Kunming, Yunnan 650032 China
- 3Department of Thoracocardiac Surgery, 920th Hospital of Joint Logistics Support Force of the Chinese People’s Liberation Army, No.212 Daguan Rd, Kunming, Yunnan 650032 China
Abstract
Background: Type 2 diabetes mellitus (T2DM) is closely associated with accelerated atherosclerosis (AS), but the molecular features linking these two conditions remain incompletely understood. This study aimed to identify candidate genes associated with T2DM and AS and to explore their potential biological relevance.
Methods: Public GEO transcriptomic datasets were analysed. GSE38642 and GSE100927 were used as T2DM and AS training datasets, while GSE41762 and GSE57691 were used for validation. Differentially expressed genes were identified using limma, and disease-associated modules were screened by weighted gene co-expression network analysis. Candidate genes were obtained by intersecting differentially expressed genes with module genes, followed by protein-protein interaction analysis, cytoHubba-MCC, and MCODE screening. Expression validation, receiver operating characteristic analysis, cross-validation, permutation testing, GeneMANIA, GSEA, ssGSEA-based immune infiltration analysis, regulatory network construction, and exploratory drug-gene enrichment analysis were performed. Selected genes were further examined in mouse models.
Results: 21 overlapping genes were identified, and six candidate hub genes were further screened. Among them, C7 and MFAP4 showed reproducible but disease-context-dependent expression patterns and exploratory discriminatory performance across the training and validation datasets. Functional analyses suggested that C7 and MFAP4 were associated with inflammatory response, complement activation, TNF-α/NF-κB signaling, oxidative phosphorylation, extracellular matrix remodeling, and immune-related alterations. Additional robustness analyses supported the exploratory relevance of these two genes, particularly MFAP4, while also indicating that the findings should be interpreted cautiously. In mouse models, C7 and MFAP4 showed disease-associated expression changes, supporting their potential relevance to metabolic stress and vascular remodeling.
Conclusion: This integrated bioinformatics and experimental validation study identified C7 and MFAP4 as exploratory candidate genes associated with T2DM and AS.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12902-026-02466-w.
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BibTeX
@article{wang2026integrated,
title = {{Integrated bioinformatics analysis and mouse validation identify C7 and MFAP4 as candidate genes associated with type 2 diabetes and atherosclerosis}},
author = {Ling Wang and Yu Chen and Peng Ding and Huaiyao Wang and Chao Wu and Peizheng Li and Chunxia Ou and Zuojing Xie and Jiannan Jin and Jie Hu and Jie Yu and Yan Wang},
journal = {BMC Endocrine Disorders},
year = {2026},
month = aug,
doi = {10.1186/s12902-026-02466-w},
url = {https://doi.org/10.1186/s12902-026-02466-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Integrated bioinformatics analysis and mouse validation identify C7 and MFAP4 as candidate genes associated with type 2 diabetes and atherosclerosis
AU - Ling Wang
AU - Yu Chen
AU - Peng Ding
AU - Huaiyao Wang
AU - Chao Wu
AU - Peizheng Li
AU - Chunxia Ou
AU - Zuojing Xie
AU - Jiannan Jin
AU - Jie Hu
AU - Jie Yu
AU - Yan Wang
PY - 2026
DA - 2026/08/06
JO - BMC Endocrine Disorders
DO - 10.1186/s12902-026-02466-w
UR - https://doi.org/10.1186/s12902-026-02466-w
AB - Background: Type 2 diabetes mellitus (T2DM) is closely associated with accelerated atherosclerosis (AS), but the molecular features linking these two conditions remain incompletely understood. This study aimed to identify candidate genes associated with T2DM and AS and to explore their potential biological relevance. Methods: Public GEO transcriptomic datasets were analysed. GSE38642 and GSE100927 were used as T2DM and AS training datasets, while GSE41762 and GSE57691 were used for validation. Differentially expressed genes were identified using limma, and disease-associated modules were screened by weighted gene co-expression network analysis. Candidate genes were obtained by intersecting differentially expressed genes with module genes, followed by protein-protein interaction analysis, cytoHubba-MCC, and MCODE screening. Expression validation, receiver operating characteristic analysis, cross-validation, permutation testing, GeneMANIA, GSEA, ssGSEA-based immune infiltration analysis, regulatory network construction, and exploratory drug-gene enrichment analysis were performed. Selected genes were further examined in mouse models. Results: 21 overlapping genes were identified, and six candidate hub genes were further screened. Among them, C7 and MFAP4 showed reproducible but disease-context-dependent expression patterns and exploratory discriminatory performance across the training and validation datasets. Functional analyses suggested that C7 and MFAP4 were associated with inflammatory response, complement activation, TNF-α/NF-κB signaling, oxidative phosphorylation, extracellular matrix remodeling, and immune-related alterations. Additional robustness analyses supported the exploratory relevance of these two genes, particularly MFAP4, while also indicating that the findings should be interpreted cautiously. In mouse models, C7 and MFAP4 showed disease-associated expression changes, supporting their potential relevance to metabolic stress and vascular remodeling. Conclusion: This integrated bioinformatics and experimental validation study identified C7 and MFAP4 as exploratory candidate genes associated with T2DM and AS. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12902-026-02466-w.
SN - 1472-6823
ER -