Shared diagnostic genes and potential mechanism between intervertebral disc degeneration and diabetes mellitus revealed by integrated transcriptomic analysis and machine learning

Bao SongWanLi Zhang^*

• Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China

Existing studies have shown a clear clinical association between intervertebral disc degeneration (IDD) and Diabetes Mellitus (DM), beyond risk factors such as mechanical stress. However, their shared molecular mechanisms remain unclear. This study conducted an integrated analysis of highthroughput sequencing data for IDD and DM.Using a protein-protein interaction (PPI) network approach, we systematically identified the shared protein regulatory network of IDD and DM. This analysis highlighted the involvement of immune-related pathways in the comorbidity of these two conditions and identified key proteins. Furthermore, a machine-learning-based screening method identified seven potential core biomarkers. Multi-cohort validation analysis recognized PRTN3 as a conserved biomarker for both IDD and DM. Pathway and immune infiltration analyses of PRTN3 in IDD and DM revealed its potential mechanism in regulating neutrophil-mediated disease processes. Experimental validation confirmed the significant upregulation of PRTN3 in patients with IDD complicated by DM. In conclusion, this study provides valuable insights into the shared pathogenic mechanisms of IDD and DM, as well as potential diagnostic biomarkers for these conditions.