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pmid:40510349

Identification and validation of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration.

Hao Li · Lei Miao · Jiayuan Wu · Ye Wang · Jiyuan Xia · Da He

Frontiers in immunology · 2025 doi:10.3389/fimmu.2025.1589849

Paper

complete

Experiment

partial

Data

partial

Analysis

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Execution

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title
Identification and validation of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration.
doi
10.3389/fimmu.2025.1589849
pmid
40510349
authors array · 6 items
[0]
Hao Li
[1]
Lei Miao
[2]
Jiayuan Wu
[3]
Ye Wang
[4]
Jiyuan Xia
[5]
Da He
journal
Frontiers in immunology
year
2025
abstract
Objective: To identify cell senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration (IVDD) using bioinformatics and investigate their biological functions and signaling pathways. Methods: GSE56081 and GSE23130 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The former was used for the analysis of differentially expressed genes (DEGs) and the latter was used as the validation set. Intersection analysis of DEGs and cell senescence-related genes was performed to screen for senescence-related differentially expressed genes (SRDEGs). SRDEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was also drawn, and the hub SRDEGs were obtained using 11 different algorithms. Immune infiltration analysis was then performed. Receiver operating characteristic (ROC) curve and quantitative polymerase chain reaction (qPCR) were used to evaluate the diagnostic value of the hub SRDEGs. Results: Four hub SRDEGs, SP1, FOXO1, ESR1, and MAPK1, were identified. SP1 was downregulated in IVDD, while the other three hub genes were upregulated. ROC curve verification showed that the AUC for SP1, FOXO1, ESR1, and MAPK1 were 0.483, 0.683, 0.683, and 0.725, respectively. RT-qPCR confirmed that MAPK1 expression was higher in the degeneration group (t = 3.229, P <0.001). Immune infiltration analysis demonstrated elevated proportions of CD8 T cells and activated NK cells in IVDD samples, with MAPK1 showing positive correlations with CD8 T cells, activated NK cells, and neutrophils but negative correlations with naive CD4 T cells, B memory cells, and resting NK cells. Conclusion: These findings highlight MAPK1 as a pivotal regulator of cellular senescence and immune cell infiltration in IVDD pathogenesis, offering novel therapeutic targets for intervention.
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The unpaired Student’s t-test was applied to assess the difference between the IVDD and control groups, and a p-value of less than 0.05 was considered to be statistically significant.
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The unpaired Student’s t-test was applied to assess the difference between the IVDD and control groups, and a p-value of less than 0.05 was considered to be statistically significant.
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RT-qPCR confirmed that MAPK1 expression was higher in the intervertebral disc degeneration group than in the control group.
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RT-qPCR confirmed the difference in MAPK1 expression in the nucleus pulposus between the degeneration and control groups, showing higher MAPK1 expression in the IVDD group (t = 3.229, P <0.001).
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sections[20] "Expression validation of hub SRDEGs" paragraph 2
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RT-qPCR confirmed the difference in MAPK1 expression in the nucleus pulposus between the degeneration and control groups, showing higher MAPK1 expression in the IVDD group (t = 3.229, P <0.001).
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RT-qPCR confirmed that MAPK1 expression was higher in the intervertebral disc degeneration group than in the control group.
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The former was used for the analysis of differentially expressed genes (DEGs) and the latter was used as the validation set. Intersection analysis of DEGs and cell senescence-related genes was performed to screen for senescence-related differentially expressed genes (SRDEGs). SRDEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was also drawn, and the hub SRDEGs were obtained using 11 different algorithms. Immune infiltration analysis was then performed. Receiver operating characteristic (ROC) curve and quantitative polymerase chain reaction (qPCR) were used to evaluate the diagnostic value of the hub SRDEGs.\nResults: Four hub SRDEGs, SP1, FOXO1, ESR1, and MAPK1, were identified. SP1 was downregulated in IVDD, while the other three hub genes were upregulated. ROC curve verification showed that the AUC for SP1, FOXO1, ESR1, and MAPK1 were 0.483, 0.683, 0.683, and 0.725, respectively. RT-qPCR confirmed that MAPK1 expression was higher in the degeneration group (t = 3.229, P <0.001). Immune infiltration analysis demonstrated elevated proportions of CD8 T cells and activated NK cells in IVDD samples, with MAPK1 showing positive correlations with CD8 T cells, activated NK cells, and neutrophils but negative correlations with naive CD4 T cells, B memory cells, and resting NK cells.\nConclusion: These findings highlight MAPK1 as a pivotal regulator of cellular senescence and immune cell infiltration in IVDD pathogenesis, offering novel therapeutic targets for intervention.", "claims": [{"id": "claim-method", "statement": "The unpaired Student’s t-test was applied to assess the difference between the IVDD and control groups, and a p-value of less than 0.05 was considered to be statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40510349", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "The unpaired Student’s t-test was applied to assess the difference between the IVDD and control groups, and a p-value of less than 0.05 was considered to be statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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