Serotonin, Dopamine, GABA, and VEGF in IDH-wildtype- Glioblastoma and Meningioma: A Comparative Study of Tissue and Serum Concentrations and Prognostic Impact

Abstract Background: IDH-wildtype Glioblastoma is the most aggressive primary brain tumor with a poor prognosis and its microenvironment influences the nervous system heavily. We investigated the levels and functional relevance of the neurotransmitters Serotonin, Dopamine, and GABA, along with Vascular Endothelial Growth Factor (VEGF), in IDH-wildtype Glioblastoma compared to the relatively benign meningioma, aiming to determine their potential as diagnostic and prognostic biomarkers. Methods: Tissue and peripheral blood samples were collected from IDH-wildtype Glioblastoma patients and meningioma controls. Concentrations of all four molecules were measured using ELISA. Statistical significance was assessed using Student's t-test (p < 0.05). The relationship between molecules was determined using Pearson's correlation, while prognostic and diagnostic potentials were evaluated via Kaplan-Meier survival analysis and Receiver Operating Characteristic (ROC) analysis, respectively. Results: Our study, statistically significant positive correlation was observed between VEGF and all three neurotransmitters (Serotonin, Dopamine, and GABA) exclusively within the tumor tissue of both IDH-wildtype Glioblastoma and meningioma patients, but this correlation was absent in peripheral blood. Kaplan-Meier analysis revealed that elevated levels of all four molecules in both tissue and blood were strongly associated with significantly shorter overall survival in IDH-wildtype Glioblastoma patients. In contrast, no significant prognostic effect was observed in meningioma patients. ROC analysis conducted to differentiate IDH-wildtype Glioblastoma from meningioma showed inferior diagnostic potential for all four molecules, both in blood and tissue. Conclusion: Our results show that neurotransmitters and VEGF are critical components of the malignant IDH-wildtype Glioblastoma microenvironment, characterized by a potent, localized neuro-angiogenic drive and poor survival outcomes. Crucially, despite their strong prognostic power in predicting survival in IDH-wildtype Glioblastoma, the peripheral and tissue concentrations of these molecules lack the necessary discriminative capacity to serve as effective standalone diagnostic biomarkers for distinguishing IDH-wildtype Glioblastoma from meningioma. We think; all of them (Dopamine, GABA, Serotonin, VEGF), the initiation and progress of IDH-wildtype Glioblastoma has led to these developments.