The Significance of Cellular Senescence Hub Genes in the Diagnosis and Subtype Classification of a Comprehensive Database of Gene Expression in Intervertebral Disc Degeneration

IF 3.4 3区医学 Q1 ORTHOPEDICS JOR Spine Pub Date : 2025-03-06 DOI:10.1002/jsp2.70050

Fei Liu, Silong Gao, Ji Yin, Chao Song, Yongliang Mei, Zhaoqiang Wang, Zongchao Liu

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Abstract

Background

Intervertebral disc degeneration (IVDD) is a complex age-related physiological process, with cellular senescence (CS) being a primary contributing factor. However, the precise role of CS and its associated genes in IVDD remains unclear.

Methods

In this study, we performed differential expression analysis on the GSE124272 and GSE150408 datasets from the GEO database and identified 53 differentially expressed cellular senescence-related genes (CSRGs). We then conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore their functions and associated pathways. We identified hub genes by constructing a protein–protein interaction (PPI) network and further validated these genes using clinical samples. We further explored the functional and prognostic significance of these genes using support vector machine recursive feature elimination (SVM-RFE), random forest (RF), and least absolute shrinkage and selection operator (LASSO) algorithms. We visualized the correlation between the differential expression levels of the four core genes and immune cell infiltration using heat maps and histograms. Finally, we performed graphene oxide enrichment analysis on 297 differentially expressed genes (DEGs) to investigate their role in IVDD.

Results

We ultimately identified four hub cellular CSRGs DUSP3, MAPKAPK5, SP1, and VEGFA, and further validated their expression using various algorithms and clinical samples. Our results revealed that DUSP3 and SP1 were upregulated in IVDD, while MAPKAPK5 and VEGFA were downregulated. Immune cell infiltration analysis demonstrated that DUSP3 and SP1 were positively correlated with immune cell infiltration levels, whereas VEGFA and MAPKAPK5 were negatively correlated.

Conclusion

In summary, CSRGs play an important role in the pathogenesis of IVDD, and our study of the hub gene cluster may guide future therapeutic strategies for IVDD.

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