Identification and Experimental Verification of Potential Immune Cell-Associated Gene Biomarkers in Human Intervertebral Disc Degeneration.

Objective: Intervertebral disc degeneration (IDD) is one of the most common diseases in the elderly population. Recently, immune disorders have been considered to play an important role in IDD. This study aimed to conduct a bioinformatic analysis to identify biomarkers associated with IDD immune cells.

Methods: We obtained the gene expression profiles of IDD by downloading the Gene Expression Omnibus Series (GSE)150408 and GSE124272 from the Gene Expression Omnibus (GEO) database. IDD and immune cell-related hub genes were identified via multiple bioinformatics analyses, and their diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. In addition, a long non-coding RNA (lncRNA)-signature gene co-expression network was constructed. Finally, the diagnostic accuracy of the biomarkers was verified using Real-time quantitative PCR (RT-qPCR).

Results: ASAP1-IT1, IKZF2, KLHL14, lnc-C10orf131-1, and LOC101927805 were identified as signature genes of IDD. Further, ROC analysis revealed that the five signature gene models had a strong ability to discriminate between the IDD and healthy control samples. We also found that the five signature genes were significantly associated with immune-inflammatory feedback, cell cycle, and skeletal system. Furthermore, an lncRNA signature gene network was constructed to reveal the regulatory mechanisms of the biomarkers. Finally, RT-qPCR results verified that IKZF2 and KLHL14 were significantly downregulated in patients with IDD, and ASAP1-IT1 was significantly upregulated.

Conclusion: This study identified ASAP1-IT1, IKZF2, and KLHL14 as the key signature genes of IDD. These key hub genes may serve as potential therapeutic targets for IDD.