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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, HIF1\u03b1, Bry, the enzyme\u00a0SOD2, and the glucose transporter GLUT1. Significant differences in protein expression were observed only in relation to Pfirrmann grade. Within the grade\u00a0III 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.<\/jats:p>","DOI":"10.1007\/s00418-025-02434-w","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T09:04:40Z","timestamp":1764061480000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunohistochemical analysis to detect a molecular signature in intervertebral disc degeneration"],"prefix":"10.1007","volume":"163","author":[{"given":"Letizia","family":"Penolazzi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Angelini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Nadalini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Chierici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Lambertini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Sief","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"De Bonis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Piva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"2434_CR1","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1002\/jor.23583","volume":"35","author":"O Alvarez-Garcia","year":"2017","unstructured":"Alvarez-Garcia O, Matsuzaki T, Olmer M, Masuda K, Lotz MK (2017) Age-related reduction in the expression of FOXO transcription factors and correlations with intervertebral disc degeneration. 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