Metabolic Reprogramming in Glioblastoma: A Rare Case of Recurrence to Scalp Metastasis

Background Glioblastoma (GB) is an aggressive malignancy with a poor prognosis, often limiting survival to 1.5-2 years. Despite standard treatment, most patients experience local recurrence within the first year, with metastasis, particularly extracranial, being exceptionally rare. The mechanisms driving GB metastasis remain poorly understood, but metabolic reprogramming has emerged as a potential factor in enhancing survival and invasiveness. This study reports a rare case of recurrent GB with scalp metastasis and explores the metabolic mechanisms behind this aggressive behavior using systems biology. Methods Tandem mass spectrometry (MS/MS) was employed to analyze amino acid profiles in both the recurrent and metastatic stages of GB. Systems biology approaches were used to uncover genetic alterations and metabolic reprogramming associated with the progression from recurrence to metastasis. Results Our analysis revealed distinct amino acid utilization patterns in a patient with a molecular phenotype of wild-type IDH-1&2, TERT mutation, non-mutated BRAF and EGFR, and non-methylated MGMT. Significant differences in amino acid profiles were observed between blood and CSF samples during recurrence and metastasis. Additionally, protein-protein interaction analysis identified key genomic drivers potentially responsible for the transition from recurrent to metastatic GB. Conclusions Beyond established risk factors such as craniotomy, biopsies, ventricular shunting, and radiation therapy, our findings suggest that metabolic reprogramming plays a crucial role in the transition from recurrent to metastatic GB. Targeting these metabolic shifts could provide new avenues for managing and preventing extracranial metastasis in GB, making this an important focus for future research.