Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis

Abstract Background Glioblastoma (GB), an aggressive brain malignancy with a poor prognosis of 1.5–2 years, rarely exhibits extracranial metastasis (ECM). However, metabolic reprogramming has emerged as a key driver of GB progression and invasiveness. This study presents a rare case of recurrent GB...

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Main Authors: Amir Barzegar Behrooz, Hamid Latifi-Navid, Narges Zolfaghari, Somayeh Piroozmand, Ahmad Pour-Rashidi, Mahsa Bourbour, Fatemeh Jusheghani, Mahmoud Aghaei, Negar Azarpira, Fatemeh Mollasalehi, Sedigheh Alamdar, Ahmad Nasimian, Jabar Lotfi, Shahla Shojaei, Elham Nazar, Saeid Ghavami
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:BJC Reports
Online Access:https://doi.org/10.1038/s44276-025-00134-5
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author Amir Barzegar Behrooz
Hamid Latifi-Navid
Narges Zolfaghari
Somayeh Piroozmand
Ahmad Pour-Rashidi
Mahsa Bourbour
Fatemeh Jusheghani
Mahmoud Aghaei
Negar Azarpira
Fatemeh Mollasalehi
Sedigheh Alamdar
Ahmad Nasimian
Jabar Lotfi
Shahla Shojaei
Elham Nazar
Saeid Ghavami
author_facet Amir Barzegar Behrooz
Hamid Latifi-Navid
Narges Zolfaghari
Somayeh Piroozmand
Ahmad Pour-Rashidi
Mahsa Bourbour
Fatemeh Jusheghani
Mahmoud Aghaei
Negar Azarpira
Fatemeh Mollasalehi
Sedigheh Alamdar
Ahmad Nasimian
Jabar Lotfi
Shahla Shojaei
Elham Nazar
Saeid Ghavami
author_sort Amir Barzegar Behrooz
collection DOAJ
description Abstract Background Glioblastoma (GB), an aggressive brain malignancy with a poor prognosis of 1.5–2 years, rarely exhibits extracranial metastasis (ECM). However, metabolic reprogramming has emerged as a key driver of GB progression and invasiveness. This study presents a rare case of recurrent GB with scalp metastasis, exploring how metabolic shifts enable GB cells to evade treatment and adapt to hostile environments, offering insights for developing innovative therapies. 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. During recurrence and metastasis, significant differences in amino acid profiles were observed between blood and cerebrospinal fluid (CSF) samples. Additionally, protein-protein interaction (PPI) 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.
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spelling doaj-art-db9cfe7f01fd4a7dbd8e2dff194d30692025-08-20T02:30:22ZengNature PortfolioBJC Reports2731-93772025-04-013111010.1038/s44276-025-00134-5Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasisAmir Barzegar Behrooz0Hamid Latifi-Navid1Narges Zolfaghari2Somayeh Piroozmand3Ahmad Pour-Rashidi4Mahsa Bourbour5Fatemeh Jusheghani6Mahmoud Aghaei7Negar Azarpira8Fatemeh Mollasalehi9Sedigheh Alamdar10Ahmad Nasimian11Jabar Lotfi12Shahla Shojaei13Elham Nazar14Saeid Ghavami15Department of Human Anatomy and Cell Science, University of Manitoba College of MedicineDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Radiology, Northwestern UniversityDepartment of Biotechnology, Alzahra UniversityDepartment of Biotechnology, Asu vanda Gene Industrial Research CompanyDepartment of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical SciencesShiraz Institute for Stem Cell and Regenerative Medicine, Shiraz University of Medical ScienceSchool of Medicine, Tehran University of Medical SciencesClinical and Anatomical Pathology Department, Milad HospitalDepartment of Human Anatomy and Cell Science, University of Manitoba College of MedicineDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Human Anatomy and Cell Science, University of Manitoba College of MedicineDepartment of Pathology, Sina Hospital, Tehran University of Medical SciencesDepartment of Human Anatomy and Cell Science, University of Manitoba College of MedicineAbstract Background Glioblastoma (GB), an aggressive brain malignancy with a poor prognosis of 1.5–2 years, rarely exhibits extracranial metastasis (ECM). However, metabolic reprogramming has emerged as a key driver of GB progression and invasiveness. This study presents a rare case of recurrent GB with scalp metastasis, exploring how metabolic shifts enable GB cells to evade treatment and adapt to hostile environments, offering insights for developing innovative therapies. 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. During recurrence and metastasis, significant differences in amino acid profiles were observed between blood and cerebrospinal fluid (CSF) samples. Additionally, protein-protein interaction (PPI) 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.https://doi.org/10.1038/s44276-025-00134-5
spellingShingle Amir Barzegar Behrooz
Hamid Latifi-Navid
Narges Zolfaghari
Somayeh Piroozmand
Ahmad Pour-Rashidi
Mahsa Bourbour
Fatemeh Jusheghani
Mahmoud Aghaei
Negar Azarpira
Fatemeh Mollasalehi
Sedigheh Alamdar
Ahmad Nasimian
Jabar Lotfi
Shahla Shojaei
Elham Nazar
Saeid Ghavami
Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis
BJC Reports
title Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis
title_full Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis
title_fullStr Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis
title_full_unstemmed Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis
title_short Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis
title_sort metabolic reprogramming in glioblastoma a rare case of recurrence to scalp metastasis
url https://doi.org/10.1038/s44276-025-00134-5
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