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A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and
Tingting Hu1, Xiaomei Duan2, Jiale Gao1
1Clinical Laboratory Center, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
Background:
T2DM and COPD are prevalent and high-burden diseases which are closely related, with poor patient outcomes. In this study, we aimed to identify common diagnostic markers for T2DM and COPD and their therapeutic potential.
Methods:
Microarray data from the GEO database were analyzed to identify DEGs, whereas WGCNA, co-differential gene analyses were employed to identify co-expression modules and DEGs functions. Diagnostic markers were determined through machine learning and validated with human blood PBMC and single-cell sequencing.
Results:
A total of 738 and 1391 DEGs were identified for T2DM and COPD, respectively. Among these, 25 key genes and 75 co-differential genes were recognized, predominantly enriched in immune-related pathways, particularly those involving T-cell signaling. Eight diagnostic markers were identified through machine learning approaches. Subsequent validation using human PBMC from three groups (Ctrl, COPD, and T2DM, n=15 each) confirmed PES1 (AUC 0.676 and 0.615), CANX (AUC 0.668 and 0.642), SUMF2 (AUC 0.684 and 0.679), and DCXR (0.625 and 0.606) as shared diagnostic markers. Analysis of single-cell sequencing data from blood and bone marrow and RT-qPCR results from healthy individuals and patients with T2DM combined with COPD showed that only SUMF2 showed a statistically significant difference in expression levels in comorbid patients and was strongly associated with T-cell subpopulations.
Conclusion:
The T-cell pathway may be involved in the pathogenesis of T2DM and COPD, and SUMF2 may be a potential diagnostic marker, and its high expression in T-cell subsets suggests a possible role in the immunomodulatory mechanisms underlying the two diseases.
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