{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T19:41:29Z","timestamp":1778614889752,"version":"3.51.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1536551","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T05:25:57Z","timestamp":1753421157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A comprehensive bioinformatics analysis of 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