Comprehensive analysis of senescence-related genes and immune infiltration in intervertebral disc degeneration: a meta-data approach utilizing bulk and single-cell RNA sequencing data

Ya-Jun Deng; Xin-Gang Wang; Zhi Li; Bo Wang; Jie Li; Jun Ma; Xiong Xue; Xin Tian; Quan-Cheng Liu; Jia-Yuan Liu; Ying Zhang; Bin Yuan

doi:10.3389/fmolb.2023.1296782

Comprehensive analysis of senescence-related genes and immune infiltration in intervertebral disc degeneration: a meta-data approach utilizing bulk and single-cell RNA sequencing data

Front Mol Biosci. 2023 Dec 22:10:1296782. doi: 10.3389/fmolb.2023.1296782. eCollection 2023.

Authors

Ya-Jun Deng¹, Xin-Gang Wang¹, Zhi Li¹, Bo Wang¹, Jie Li¹, Jun Ma¹, Xiong Xue¹, Xin Tian¹, Quan-Cheng Liu¹, Jia-Yuan Liu¹, Ying Zhang¹, Bin Yuan¹

Affiliation

¹ Department of Spine Surgery, Xi'an Daxing Hospital, Yanan University, Xi'an, China.

Abstract

Objectives: This study aims to identify the key senescence genes and potential regulatory mechanisms that contribute to the etiology of intervertebral disc degeneration (IDD). Method: We analyzed GSE34095 and GSE70362 datasets, identifying key senescence-related differentially expressed genes (DEGs) in IDD using lasso regression. Risk scores classified patients into high- and low-risk groups. We compared pathways, functions, and immune infiltration between these groups. Diagnostic ability was assessed using ROC curves and a nomogram predicted IDD incidence. In single-cell dataset GSE165722, we evaluated expression of key senescence-related DEGs. Results: We identified 12 key senescence-related DEGs distinguishing high- and low-risk IDD patients. Enrichment analysis revealed cellular stress response, apoptotic signaling pathway, and protein kinase activation differences. Immune cell analysis showed elevated eosinophils in low-risk group and increased effector memory CD8 T, central memory CD4 T, myeloid-derived suppressor, natural killer, monocyte, Type 1 T helper, plasmacytoid dendritic, and natural killer T cells in high-risk group. A nomogram using AUC >0.75 genes (CXCL8, MAP4K4, MINK1, and TNIK) predicted IDD incidence with good diagnostic power. High senescence scores were observed in neutrophils. Conclusion: Our diagnostic model, based on key senescence-related DEGs and immune cell infiltration, offers new insights into IDD pathogenesis and immunotherapy strategies.

Keywords: immune infiltration; intervertebral disc degeneration; risk score; senescence-related genes; single-cell.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Science Foundation of China (No. 82260443).