Plasma Proteomic Profiling Identifies a Six-Protein Panel for Grading and Predicting Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) represents a significant health concern affecting a large portion of the population and leads to chronic pain and disability. Despite the prevalence of this condition, the underlying biological mechanisms and potential biomarkers for early diagnosis remain inadequately understood. Advances in proteomics have opened new avenues for identifying blood biomarkers that can facilitate better diagnostic and therapeutic strategies. The primary aim of this study was to identify and validate specific plasma proteins associated with varying grades of IDD. This case-control study compared plasma samples from patients with grade II (n = 10) and grade V (n = 10) IDD to assess differential protein expression. Proteomic analysis was conducted via the SomaScan Assay to screen and identify candidate proteins. Six differential proteins─COL6α3, REG1β, ATF5, CAP1, MAGEA4, and LILRB3─were identified with the highest fold changes and recognized as biomarkers. Subsequent validation of these biomarkers was performed using enzyme-linked immunosorbent assay (ELISA) technology in a validation cohort of 50 patients. A final six-protein combined model achieved an optimal predictive efficacy (AUC = 0.8700). This study provides several noninvasive and rapid plasma biomarkers for the early diagnosis of IDD.