Gasdermin as a Molecular Signature and Predictor of Adult-Type Diffuse Glioma Severity and Grading

Background/Objectives: Gasdermin D (GSDMD) is a critical mediator of pyroptosis-an inflammatory form of programmed cell death increasingly implicated in tumor biology. Our objective was to evaluate the utility of GSDMD as a diagnostic and prognostic biomarker and to investigate its association with tumor burden and hematological parameters. Methods: We analyzed GSDMD expression levels in patients with adult-type diffuse gliomas compared to healthy controls and assessed correlations with tumor size, histological grade, hematological markers, and survival outcomes. Data was complemented by transcriptomic analysis from The Cancer Genome Atlas (TCGA). Diagnostic performance was assessed using ROC curve analysis. Results: GSDMD expression was significantly elevated in adult-type diffuse glioma patients and increased with tumor grade, suggesting an association with disease severity. A positive correlation was observed between GSDMD level and tumor size (R = 0.332; p = 0.01). ROC analysis showed moderate classification ability (AUC = 0.657) with high specificity (96%), supporting its diagnostic potential. Survival analysis showed that higher GSDMD expression was associated with reduced disease-specific survival. GSDMD also correlated positively with the erythrocyte parameter mean corpuscular hemoglobin (MCH, R = 0.34, p = 0.016) and negatively with the systemic inflammatory marker C-reactive protein (CRP, R = -0.32; p = 0.042). TCGA data showed no significant sex-related differences in GSDMD expression. Baseline characteristics such as age, BMI, and coagulation parameters were matched between patients and controls. Conclusions: GSDMD is significantly associated with astrocytoma severity, tumor size, and inflammatory status, with elevated expression indicating a worse prognosis. Its correlation with tumor grade, survival and high specificity in distinguishing patients from healthy individuals, underlines its promise as a clinically relevant, non-sex-specific biomarker for diagnosis and monitoring.