Identification and validation of potential biomarkers associated with RNA modification-related gene signatures in intervertebral disc degeneration

Intervertebral disc degeneration (IDD) represents a prevalent degenerative disorder. Accumulating evidence indicates the involvement of RNA modification-related genes in IDD pathogenesis, although the underlying mechanisms remain unclear. This study integrated public IDD datasets with RNA modification-related genes from existing literature and key module genes identified through weighted gene co-expression network analysis, yielding 105 candidate genes. Of these, 102 exhibited protein-protein interactions, with core genes primarily enriched in protein processing and axon guidance pathways. Further screening using Boruta and XGBoost identified seven candidate biomarkers.​ Among the seven candidate biomarkers, TFPI and TNFAIP6​ were consistently upregulated in IDD samples across datasets. A nomogram constructed from these potential biomarkers achieved an AUC value of 0.953 in the GSE70362 dataset, and independent external clinical validation is still needed to verify its diagnostic performance prior to clinical application. Functional enrichment analysis suggested that TFPI and TNFAIP6 are potentially associated with mismatch repair, cytokine interactions, and immune-related processes. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in a small clinical cohort provided supportive experimental evidence for the upregulation of TFPI and TNFAIP6. Collectively, these findings suggest that TFPI and TNFAIP6 may serve as potential biomarkers for IDD, while their biological functions necessitate further in-depth investigation specific to IDD.