Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning

IntroductionIntervertebral disc degeneration (IDD) and diabetes mellitus (DM) are clinically associated beyond traditional risk factors, yet the shared molecular mechanisms remain unclear.MethodsWe integrated transcriptomic data from IDD and DM cohorts, performed differential expression and protein–...

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Main Authors: Bao Song, Jianmin Wang, Hao Tang, Huadong Li, Wanli Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1576826/full
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author Bao Song
Jianmin Wang
Hao Tang
Huadong Li
Wanli Zhang
author_facet Bao Song
Jianmin Wang
Hao Tang
Huadong Li
Wanli Zhang
author_sort Bao Song
collection DOAJ
description IntroductionIntervertebral disc degeneration (IDD) and diabetes mellitus (DM) are clinically associated beyond traditional risk factors, yet the shared molecular mechanisms remain unclear.MethodsWe integrated transcriptomic data from IDD and DM cohorts, performed differential expression and protein–protein interaction (PPI) network analyses, and applied machine learning to identify shared diagnostic genes. Pathway enrichment, immune infiltration analyses, and experimental qPCR validation were conducted to explore mechanisms and confirm findings.ResultsWe identified 138 shared differentially expressed genes enriched in immune-related pathways. Seven hub genes, including PRTN3, were identified by Random Forest models. PRTN3 showed consistent upregulation across discovery, validation, and internal cohorts. Pathway and immune analyses revealed strong associations between PRTN3 expression and neutrophil-related processes in both IDD and DM. Experimental validation confirmed PRTN3 upregulation in blood samples from patients with concurrent IDD and DM.DiscussionOur findings suggest that immune-inflammatory mechanisms, particularly involving neutrophils, underlie the comorbidity between IDD and DM. PRTN3 emerges as a promising shared diagnostic biomarker and potential therapeutic target for these conditions.
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spelling doaj-art-70680665a16c49d69cdf1d2d63d20f8f2025-07-18T04:10:19ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.15768261576826Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learningBao SongJianmin WangHao TangHuadong LiWanli ZhangIntroductionIntervertebral disc degeneration (IDD) and diabetes mellitus (DM) are clinically associated beyond traditional risk factors, yet the shared molecular mechanisms remain unclear.MethodsWe integrated transcriptomic data from IDD and DM cohorts, performed differential expression and protein–protein interaction (PPI) network analyses, and applied machine learning to identify shared diagnostic genes. Pathway enrichment, immune infiltration analyses, and experimental qPCR validation were conducted to explore mechanisms and confirm findings.ResultsWe identified 138 shared differentially expressed genes enriched in immune-related pathways. Seven hub genes, including PRTN3, were identified by Random Forest models. PRTN3 showed consistent upregulation across discovery, validation, and internal cohorts. Pathway and immune analyses revealed strong associations between PRTN3 expression and neutrophil-related processes in both IDD and DM. Experimental validation confirmed PRTN3 upregulation in blood samples from patients with concurrent IDD and DM.DiscussionOur findings suggest that immune-inflammatory mechanisms, particularly involving neutrophils, underlie the comorbidity between IDD and DM. PRTN3 emerges as a promising shared diagnostic biomarker and potential therapeutic target for these conditions.https://www.frontiersin.org/articles/10.3389/fendo.2025.1576826/fullintervertebral disc degenerationdiabetes mellitusPRTN3diagnosticimmune infiltration
spellingShingle Bao Song
Jianmin Wang
Hao Tang
Huadong Li
Wanli Zhang
Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
Frontiers in Endocrinology
intervertebral disc degeneration
diabetes mellitus
PRTN3
diagnostic
immune infiltration
title Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
title_full Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
title_fullStr Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
title_full_unstemmed Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
title_short Shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
title_sort shared diagnostic genes and potential mechanisms between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning
topic intervertebral disc degeneration
diabetes mellitus
PRTN3
diagnostic
immune infiltration
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1576826/full
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