A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease

BackgroundT2DM 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.MethodsMicroarray data from the GEO database were analyzed to identify...

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Main Authors: Tingting Hu, Xiaomei Duan, Jiale Gao, Zheng Li, Dan Xu, Jing Jing, Fengsen Li, Jianbing Ding, Li Ma, Min Jiang, Jing Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1536551/full
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author Tingting Hu
Xiaomei Duan
Jiale Gao
Zheng Li
Dan Xu
Jing Jing
Fengsen Li
Jianbing Ding
Li Ma
Min Jiang
Jing Wang
author_facet Tingting Hu
Xiaomei Duan
Jiale Gao
Zheng Li
Dan Xu
Jing Jing
Fengsen Li
Jianbing Ding
Li Ma
Min Jiang
Jing Wang
author_sort Tingting Hu
collection DOAJ
description BackgroundT2DM 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.MethodsMicroarray 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.ResultsA 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.ConclusionThe 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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spelling doaj-art-32bc1f8b208c433c83015beb4e96ffbd2025-08-20T03:55:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15365511536551A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary diseaseTingting Hu0Xiaomei Duan1Jiale Gao2Zheng Li3Dan Xu4Jing Jing5Fengsen Li6Jianbing Ding7Li Ma8Min Jiang9Jing Wang10Clinical Laboratory Center, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaClinical Laboratory Center, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaDepartment of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, ChinaDepartment of Endocrinology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaXinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaBackgroundT2DM 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.MethodsMicroarray 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.ResultsA 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1536551/fulltype 2 diabetes mellitusChronic Obstructive Pulmonary Diseaseweighted gene co-expression network analysismachine learningsingle-cell sequencingSUMF2
spellingShingle Tingting Hu
Xiaomei Duan
Jiale Gao
Zheng Li
Dan Xu
Jing Jing
Fengsen Li
Jianbing Ding
Li Ma
Min Jiang
Jing Wang
A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
Frontiers in Immunology
type 2 diabetes mellitus
Chronic Obstructive Pulmonary Disease
weighted gene co-expression network analysis
machine learning
single-cell sequencing
SUMF2
title A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
title_full A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
title_fullStr A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
title_full_unstemmed A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
title_short A comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
title_sort comprehensive bioinformatics analysis of pathways and biomarkers shared between type 2 diabetes mellitus and chronic obstructive pulmonary disease
topic type 2 diabetes mellitus
Chronic Obstructive Pulmonary Disease
weighted gene co-expression network analysis
machine learning
single-cell sequencing
SUMF2
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1536551/full
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