Asparagine-related biomarkers and regulatory mechanisms in type 2 diabetes mellitus - Original Research

Sep 28, 2026

Uploaded by Margaret

Type 2 diabetes mellitus is a complex metabolic disorder in which asparagine metabolism may contribute to disease development, yet the underlying molecular basis remains unclear. This original research analyzes peripheral blood transcriptomic datasets from patients and controls using differential expression, PPI networks, machine learning biomarker screening, and cross-cohort validation. Immune infiltration and multi-layer regulatory network construction are performed, while drug-target interaction and molecular docking guide therapeutic prioritization. PPP1CA and CTSD are validated as biomarkers and link immune-metabolic crosstalk with diagnostic value and candidate compounds for intervention.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Methods

Results

Conclusion

TYPE Original Research PUBLISHED 17 December 2025 DOI 10.3389/fmolb.2025.1733878 OPEN ACCESS EDITED BY Xiaoyan Xing, Chinese Academy of Medical Sciences and Peking Union Medical College, China REVIEWED BY Zhuolun Sun, Ludwig Maximilian University of Munich, Germany Fahui Liu, Xiamen University, China *CORRESPONDENCE Bo Cao, [Caobo39666@163.com](Caobo39666@163.com)[ ](Caobo39666@163.com)Mingming Kong, [826168886@qq.com](826168886@qq.com)[ ](826168886@qq.com)RECEIVED 28 October 2025 REVISED 24 November 2025 ACCEPTED 01 December 2025 PUBLISHED 17 December 2025 CITATION Xia J, Cai T, Chen P, Gan L, Cao B and Kong M (2025) Asparagine-related biomarkers and regulatory mechanisms in type 2 diabetes mellitus. Front. Mol. Biosci. 12:1733878 . doi: 10.3389/fmolb.2025.1733878 COPYRIGHT © 2025 Xia, Cai, Chen, Gan, Cao and Kong. 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) and the copyright owner(s) 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. Asparagine-related biomarkers and regulatory mechanisms in type 2 diabetes mellitus Jiayi Xia 1, Tao Cai 2, Peiyin Chen 3, Lu Gan 1, Bo Cao 2* and Mingming Kong 4* 1 Department of Endocrinology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China, 2 Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China, 3 Department of Endocrinology, The Second People’s Hospital of Guizhou Provincial, Guiyang, Guizhou, China, 4Outpatient Department, The 970th Hospital of PLA Joint Logistic Support Force, Yantai, Shandong, China Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder. Emerging evidence suggests asparagine metabolism might play a pivotal role in T2DM, yet the underlying molecular mechanisms remain elusive. This study aimed to detect asparagine-related biomarkers and expound their functional roles in T2DM pathogenesis. Methods: Transcriptomic datasets from peripheral blood samples of T2DM patients and controls were analyzed. Differential expression analysis, proteinprotein interaction (PPI) network, and machine learning algorithms, followed by expression analysis across cohorts were employed to screen biomarkers. Biomarker diagnostic performance was evaluated. Functional enrichment, immune infiltration analysis, and multi-layer regulatory network construction were conducted. Drug-target interactions and molecular docking were explored to identify potential therapeutics. Results: A total of 90 candidate genes were detected. Four feature genes were screened via multi-algorithm integration. Protein phosphatase 1 catalytic subunit alpha (PPP1CA) and cathepsin D (CTSD) were validated as biomarkers, showing significant upregulation inT2DM samples and high diagnostic accuracy (AUC of PPP1CA = 0.969 and CTSD = 0.984 in the training cohort, AUC of PPP1CA = 0.806 and CTSD = 0.875 in the validation cohort, respectively) . Functional enrichment highlighted distinct yet complementary functional roles of PPP1CAand CTSD inT2DM progression. Immune infiltration revealed elevated activated dendritic cells, mast cells, and myeloid-derived suppressor cells in T2DM samples, with PPP1CA and CTSD correlating significantly with these cell types. Regulatory networks identified shared transcription factors and miRNAs targeting both genes. Pharmacological screening prioritized norcantharidin andnaringenin as high-affinity compounds targeting these biomarkers. Conclusion: This study identified PPP1CA and CTSD as asparagine-related biomarkers driving immune-metabolic crosstalk i

FAQs

What was the main objective of the study?

To detect asparagine-related biomarkers and clarify their functional roles in type 2 diabetes mellitus pathogenesis.

How were candidate biomarkers screened and validated?

Transcriptomic data from peripheral blood were analyzed using differential expression, protein-protein interaction networks, and machine-learning integration, followed by expression validation across cohorts and diagnostic performance evaluation.

Which biomarkers were finally validated, and what diagnostic performance did they show?

PPP1CA and CTSD were validated as biomarkers with significant upregulation in T2DM samples and high diagnostic accuracy, including AUC values reported for both training and validation cohorts.

What therapeutic candidates were prioritized in the study?

Pharmacological screening prioritized norcantharidin and naringenin as high-affinity compounds targeting the identified biomarkers, supported by drug-target interaction and molecular docking analyses.

Sep 28, 2026

Uploaded by Margaret