Unveiling key genes for intervertebral disc degeneration prediction and potential drug discovery

Gene alteration plays key role in the pathogenesis of intervertebral disc degeneration (IDD). This study aimed to explore the genes related to IDD, and identified potential therapeutic drugs for IDD treatment. Three gene profile datasets of the IDD were used to identified key genes related to IDD pathogenesis. A scRNA-seq dataset of IDD was used to examine the expression of key genes. A diagnostic model for IDD was constructed and validated by external dataset. Functional enrichment analysis was performed for diagnostic model. Connectivity Map (CMap) database was used to identify potential drugs for IDD based on the genes. The clinical samples of discs tissues were applied to test the expression of genes by immunohistochemistry (IHC) staining. Three genes (ELMO1, CKAP4, and SACM1L) were highly expressed in IDD tissues after overlapping DEGs from three gene datasets. The scRNA-seq dataset results revealed that these three genes were high expression in nucleus pulposus cells of severe IDD. A diagnostic model was constructed based on the three genes, and showed high diagnostic value. Functional enrichment analysis revealed the biological function and pathways of model related genes. CMap database and molecular docking revealed that several candidate drug for IDD treatment. The IHC results from clinical disc samples confirmed the elevation of the three genes in IDD tissues. The ELMO1, CKAP4, and SACM1L were critical genes to the pathogenesis of IDD. The diagnostic model using these three genes demonstrated high accuracy for IDD diagnosis, and identified several candidate drugs for IDD treatment.