Background: Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD).
Methods: GSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA-gene and transcription factor-gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed.
Results: A total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted.
Conclusion: This study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications.
Keywords: Autophagy; Diagnostic model; Immune cells infiltration; Intervertebral disc degeneration.
© 2023. The Author(s).