Immunohistochemical analysis to detect a molecular signature in intervertebral disc degeneration

TL;DR

This study explores molecular markers in intervertebral disc degeneration to better understand patient-specific factors influencing outcomes.

Contribution

The study identifies a molecular signature in intervertebral disc degeneration that correlates with Pfirrmann grade but not with patient-specific clinical outcomes.

Findings

Protein expression levels in intervertebral disc biopsies varied significantly with Pfirrmann grade.

No correlation was found between protein expression and patient-specific clinical outcomes like pain or healing.

Comprehensive data collection is needed to understand individual patient responses to disc degeneration.

Abstract

Intervertebral disc degeneration (IDD) is known as a primary contributor to low back pain, a debilitating condition which is the leading cause of disability worldwide. Traditionally, its assessment is based on clinical parameters, including magnetic resonance imaging (MRI). However, patients with similar radiological findings may have significantly different prognoses suggesting the involvement of patient-specific biomarkers and little-investigated molecules supporting the complexity of the pathophysiological microenvironment of the intervertebral disc (IVD). We conducted a study on IVD biopsies from 40 patients with mild IDD (Pfirrmann III), to identify a potential molecular signature that correlates with clinical and behavioral parameters including sex, age, smoking, body mass index (BMI), duration of symptoms prior to surgery, inflammatory cell density, or surgical site. Immunohistological analysis focused on the expression of proteins involved in the defense against oxidative stress, in the maintenance of IVD homeostasis, and energy metabolism: the transcription factors FOXO3a, HIF1α, Bry, the enzyme SOD2, and the glucose transporter GLUT1. Significant differences in protein expression were observed only in relation to Pfirrmann grade. Within the grade III subgroup, expression levels did not vary with patient-specific parameters or clinical outcomes such as complete healing, recurrence, or persistent pain after surgery. This highlights the importance of broadening the scope of assessment in pathological conditions such as IDD. Rather than limiting the evaluation to the expression level of a single protein marker, it is crucial to collect comprehensive data on the various factors that may influence individual patient responses to disc degeneration.

The online version contains supplementary material available at 10.1007/s00418-025-02434-w.

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