ORIGINAL RESEARCH article

Front. Immunol.

Sec. Systems Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1536551

This article is part of the Research TopicExploring the Immune-Metabolic Network in DiabetesView all 6 articles

A Comprehensive Bioinformatics Analysis of Pathways and Biomarkers Shared Between Type 2 Diabetes Mellitus and Chronic Obstructive Pulmonary Disease

Provisionally accepted
Tingting  HuTingting Hu1Xiaomei  DuanXiaomei Duan1Jiale  GaoJiale Gao1Zheng  LiZheng Li1Dan  XuDan Xu1Jing  JingJing Jing1Fengsen  LiFengsen Li1Jianbing  DingJianbing Ding2Li  MaLi Ma1Min  JiangMin Jiang1*Jing  WangJing Wang1*
  • 1Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, 乌鲁木齐市, China
  • 2Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Region, China

The final, formatted version of the article will be published soon.

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 immunerelated 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.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.

Keywords: type 2 diabetes mellitus, chronic obstructive pulmonary disease, weighted gene co-expression network analysis, machine learning, single-cell sequencing, SUMF2

Received: 13 Dec 2024; Accepted: 08 Jul 2025.

Copyright: © 2025 Hu, Duan, Gao, Li, Xu, Jing, Li, Ding, Ma, Jiang and Wang. 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:
Min Jiang, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, 乌鲁木齐市, China
Jing Wang, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, 乌鲁木齐市, China

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