ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1606905
This article is part of the Research TopicRegulation of intervertebral disc homeostasis and the pathological or pathophysiological alterations under various harmful stimuli during aging processView all 11 articles
Role of hypoxia-related genes and immune infiltration in intervertebral disc degeneration: molecular mechanisms and diagnostic potential
Provisionally accepted
- 1Department of Orthopedics(Spine), First People's Hospital of Chongqing Liangjiang New District, Chongqing, China
- 2Department of Orthopaedic Surgery, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- 3Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Objective: To investigate the role of hypoxia-related genes and immune infiltration in intervertebral disc degeneration (IDD) to identify molecular mechanisms and potential therapeutic targets.Methods: Using GEO data, IDD-related gene expression datasets were analyzed for hypoxiarelated differentially expressed genes (HRDEGs). Logistic regression and receiver operating characteristic (ROC) analyses were employed to evaluate the diagnostic potential of HRDEGs.Consensus clustering further delineated molecular subtypes of IDD. Functional enrichment analyses (GO, KEGG, GSEA) highlighted key pathways. Protein-protein interaction (PPI) networks were built in STRING and visualized with Cytoscape, identifying core genes with MCODE and CytoHubba. Immune cell infiltration was analyzed with CIBERSORT and ssGSEA to correlate immune cells with hypoxia-related genes. To validate the expression of potential biomarkers, qPCR and immunohistochemistry were conducted on human intervertebral disc tissue samples.The integration of GSE150408 and GSE124272 datasets with batch effect removal enabled differential gene analysis, identifying nine HRDEGs, including RCOR2, STAT3, and NOTCH1. Logistic regression analysis demonstrated that these genes have high diagnostic efficacy for IDD. Co-expression and clustering analyses revealed two distinct molecular subtypes in IDD, each characterized by unique gene expression and immune infiltration profiles. Functional and pathway enrichment analyses also showed that these DEGs are involved in pathways regulating TP53 transcription, oxidative phosphorylation, and MAPK signaling, contributing to IDD pathology. Conclusions: Hypoxia-related genes, particularly RCOR2, STAT3, and NOTCH1, play a significant role in the pathology of IDD and may serve as valuable diagnostic biomarkers and therapeutic targets, with distinct immune infiltration patterns associated with different IDD subtypes.
Keywords: hypoxia, Intervertebral Disc Degeneration, biomarkers, Immune infiltration, Gene Expression
Received: 06 Apr 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Zhou, Zhou, Luo, Chen, Ao, Wu, Yang and He. 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:
Bo Yang, Department of Orthopedics(Spine), First People's Hospital of Chongqing Liangjiang New District, Chongqing, China
Zhongyuan He, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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