Arginase 1 as a candidate immune-metabolic biomarker in lumbar disc herniation: integrated bioinformatics, experimental validation, and clinical evidence.

This study aimed to identify a candidate immune-related biomarker for lumbar disc herniation (LDH) and examine the functional relevance of ARG1 in intervertebral disc degeneration. Bioinformatics analysis was performed using the GSE146904 transcriptomic dataset to identify differentially expressed genes (DEGs) and determine the core target. A puncture-induced rat disc degeneration model was then established, followed by in vivo ARG1 gain- and loss-of-function interventions. In vitro assays were used to evaluate the effects of ARG1 on chondrocyte biological behavior, extracellular matrix metabolism, inflammatory responses, and arginine metabolism. In addition, 57 patients with LDH and 68 healthy controls were retrospectively enrolled to assess the diagnostic value of serum ARG1. After multidimensional screening of the high-effect candidate DEGs, ARG1 was the only gene that met the prespecified immune-process, immune-pathway, and skeletal-system annotation criteria and was therefore prioritized for experimental validation. ARG1 was expressed at a low level in degenerated intervertebral disc tissues. ARG1 up-regulation attenuated puncture-induced disc injury and pain sensitization, promoted chondrocyte proliferation, inhibited apoptosis, increased SOX9 and COL2A1 expression, and reduced MMP13 and ADAMTS5 expression. Clinical testing showed that serum ARG1 levels were reduced in patients with LDH and were negatively correlated with Pfirrmann grade and VAS pain score. The area under the curve of serum ARG1 for distinguishing patients with LDH from healthy controls was 0.818. ARG1 was associated with attenuation of puncture-induced disc injury and early degenerative changes and may serve as a candidate auxiliary serum biomarker for LDH assessment and a potential target for future studies of immune-metabolic regulation.