Metabolic remodeling in glioblastoma: a longitudinal multi-omics study.


Journal

Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673

Informations de publication

Date de publication:
12 Oct 2024
Historique:
received: 07 07 2024
accepted: 06 09 2024
medline: 12 10 2024
pubmed: 12 10 2024
entrez: 11 10 2024
Statut: epublish

Résumé

Monitoring tumor evolution and predicting survival using non-invasive liquid biopsy is an unmet need for glioblastoma patients. The era of proteomics and metabolomics blood analyzes, may help in this context. A case-control study was conducted. Patients were included in the GLIOPLAK trial (ClinicalTrials.gov Identifier: NCT02617745), a prospective bicentric study conducted between November 2015 and December 2022. Patients underwent biopsy alone and received radiotherapy and temozolomide. Blood samples were collected at three different time points: before and after concomitant radiochemotherapy, and at the time of tumor progression. Plasma samples from patients and controls were analyzed using metabolomics and proteomics, generating 371 omics features. Descriptive, differential, and predictive analyses were performed to assess the relationship between plasma omics feature levels and patient outcome. Diagnostic performance and longitudinal variations were also analyzed. The study included 67 subjects (34 patients and 33 controls). A significant differential expression of metabolites and proteins between patients and controls was observed. Predictive models using omics features showed high accuracy in distinguishing patients from controls. Longitudinal analysis revealed temporal variations in a few omics features including CD22, CXCL13, EGF, IL6, GZMH, KLK4, and TNFRSP6B. Survival analysis identified 77 omics features significantly associated with OS, with ERBB2 and ITGAV consistently linked to OS at all timepoints. Pathway analysis revealed dynamic oncogenic pathways involved in glioblastoma progression. This study provides insights into the potential of plasma omics features as biomarkers for glioblastoma diagnosis, progression and overall survival. Clinical implication should now be explored in dedicated prospective trials.

Identifiants

pubmed: 39394177
doi: 10.1186/s40478-024-01861-5
pii: 10.1186/s40478-024-01861-5
doi:

Substances chimiques

Biomarkers, Tumor 0

Banques de données

ClinicalTrials.gov
['NCT02617745']

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

162

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Maxime Fontanilles (M)

INSERM U1245, Cancer and Brain Genomics, IRON group, Normandie Univ, UNIROUEN, Rouen, France. maxime.fontanilles@chb.unicancer.fr.
Department of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France. maxime.fontanilles@chb.unicancer.fr.

Jean-David Heisbourg (JD)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Arthur Daban (A)

Department of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France.

Frederic Di Fiore (F)

Department of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France.

Louis-Ferdinand Pépin (LF)

Clinical Research Unit, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France.

Florent Marguet (F)

Department of Pathology, Normandy Centre for Genomic and Personalized Medicine, INSERM U1245, CHU Rouen, Normandie Univ, UNIROUEN, 1 Rue de Germont, 76031, Rouen Cedex, France.

Olivier Langlois (O)

Department of Neurosurgery, CHU Rouen, 76000, Rouen, France.

Cristina Alexandru (C)

Department of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France.

Isabelle Tennevet (I)

Department of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France.

Franklin Ducatez (F)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.
INSERM U1245, Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Carine Pilon (C)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Thomas Plichet (T)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Déborah Mokbel (D)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Céline Lesueur (C)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Soumeya Bekri (S)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

Abdellah Tebani (A)

INSERM U1245, Department of Metabolic Biochemistry, Normandie Univ, UNIROUEN, CHU Rouen, 76000, Rouen, France.

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