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Significance of Oxidative Stress in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration

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Abstract

Intervertebral disc degeneration (IVDD) is a common illness of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance in the production and catabolism of extracellular matrix, and an inflammatory response. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or raises the formation of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 OS-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408. Then, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1) from 35 DEGs, and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to forecast the risk of IVDD patients, we developed a nomogram. We obtained two OSRG clusters (clusters A and B) by consensus clustering based on the six hub genes. Then, 3147 DEGs were obtained by differential expression analysis in the two clusters, and all samples were further divided into two gene clusters (A and B). We investigated differences in immune cell infiltration levels between different clusters and found that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. In conclusion, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.

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Funding

Natural Science Fund Committee of Jiangsu Provincial, BK20221420, Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine, ZD202008.

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Authors and Affiliations

  1. Department of Spine Surgery, Third Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China

    Jun Gu, Xiaoyang Zhou & Lin Xie

  2. Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine for Nanjing University of Chinese Medicine, Nanjing, 210028, China

    Jun Gu, Xiaoyang Zhou & Lin Xie

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  1. Jun Gu
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  2. Xiaoyang Zhou
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The authors confifirm contribution to the paper as follows: study conception, design, data collection and draft manuscript preparation: Jun Gu, Xiaoyang Zhou; analysis and interpretation of results: Lin Xie. All authors reviewed the results and approved the fifinal version of the manuscript.

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Correspondence to Lin Xie.

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10528_2023_10412_MOESM1_ESM.tif

Supplementary file1 (TIF 9984 kb): Supplementary Figure 1 35 differentially expressed OSRGs were imported into the STRING protein database with a minimum interaction score of 0.15 as the threshold. The network contains 35 nodes and 167 edges

10528_2023_10412_MOESM2_ESM.tif

Supplementary file2 (TIF 25511 kb): Supplementary Figure 2 The AUC values of ATP7A, MELK, NCF1, NOX1, RHOB, and SP1 were 0.748, 0.717, 0.800, 0.726, 0.776, and 0.789, demonstrating the high accuracy and predictive utility of the six hub OSRGs

10528_2023_10412_MOESM3_ESM.tif

Supplementary file3 (TIF 18933 kb): Supplementary Figure 3 (A-G) Consensus matrices of the six hub OSRGs for k = 3-9. (H and I) The CDF plot and the consensus clustering matrix's delta area

10528_2023_10412_MOESM4_ESM.tif

Supplementary file4 (TIF 19079 kb): Supplementary Figure 4 (A-G) Consensus matrices of the 3147 DEGs for k = 3-9. (H and I) The CDF plot and the consensus clustering matrix's delta area

10528_2023_10412_MOESM5_ESM.xlsx

Supplementary file5 (XLSX 98 kb): Supplementary Table 1 From the GSEA database, we obtained 437 OSRGs based on C5 - GO:BP - GOBP_RESPONSE_TO_OXIDATIVE_STRESS

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Gu, J., Zhou, X. & Xie, L. Significance of Oxidative Stress in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration. Biochem Genet 62, 193–207 (2024). https://doi.org/10.1007/s10528-023-10412-x

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