Profiles of Short Chain Fatty Acid Metabolism as Genetic Biomarkers for Primary Brain Gliomas

20 May 2024, 18:10
5m
La Biodola, Isola d'Elba

La Biodola, Isola d'Elba

Hotel Hermitage
Poster Next-gen clinical PET/CT Poster Session

Speaker

Marianna Inglese (Department of Biomedicine and Prevention, University of Rome Tor Vergata)

Description

Genetic factors play a crucial role in diagnosis and treatment of glioblastoma multiforme (GBM). The key biomarker, isocitrate dehydrogenase (IDH), is associated with better survival rates in its mutated forms than in wild-type. GBM diagnosis is complex due to tumor heterogeneity and risks in sampling, and this highlights the need for non-invasive diagnostic methods. We examined the impact of glioma-specific short chain fatty acid (SCFA) transcellular flux mechanisms for energy production on genotypes and patient survival. We analyzed the genetic profiles of 10 GBM patients (5 mutants and 5 wild-types) using dynamic 18F-fluoropivalate (FPIA) PET scans focusing on 25,202(±14,337) time activity curves(TACs). We identified four distinct metabolic SCFA oxidation profiles within the lesion through time-series k-means clustering and then used deep learning to associate them with GBM genotypes. Our model accurately differentiated mutant and wild-type GBMs with a 96.75%(±3.24) accuracy, when used features extracted from the combination of the first 2 clusters’ TACs only. However, its effectiveness significantly decreased when ignoring SCFA metabolism heterogeneity (i.e. the clustered metabolic profiles), as shown by the lower accuracy rates obtained using the full range of FPIA TACs(70.42%±16.25). Of note, the TACs belonging to the cluster with the lowest FPIA SUV, showed the worst performance (23.67%(±16.83)acc) confirming SCFA metabolism to be a potential biomarker of GBM genotype.

Field Software and quantification

Primary author

Marianna Inglese (Department of Biomedicine and Prevention, University of Rome Tor Vergata)

Co-authors

Mr Tommaso Boccato (University of Rome Tor Vergata, Department of Biomedicine and Prevention) Mr Matteo Ferrante (University of Rome Tor Vergata, Department of Biomedicine and Prevention) Mr Shah Islam (Department of Surgery and Cancer, Imperial College London, London, United Kingdom) Dr Matthew Williams (Computational Oncology Group, Department of Surgery and Cancer, Imperial College London, London, UK) Prof. Adam D Waldman (Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK) Dr Kevin O'Neill (Imperial College Healthcare NHS Trust, London) Prof. Eric O Aboagye (Department of Surgery and Cancer, Imperial College London, London, United Kingdom) Prof. Nicola Toschi (University of Rome Tor Vergata, Department of Biomedicine and Prevention)

Presentation materials