Molecular tumour profiling of glioblastoma using mass spectrometry imaging

  • Matthew Gentry

Student thesis: Phd


Glioblastoma (GBM) is the most common and most aggressive primary brain tumour, with an extremely poor prognosis. Despite extensive research into this aggressive tumour, overall survival has been unaffected in the past 15 years with average survival at 12-15 months with optimal standard of care treatment. Glioblastoma tumour cells exhibit strong proliferative and infiltrative characteristics, which contributes to the infiltration of tumour cells into healthy brain. This feature means safe total resection of all tumour cells is impossible, which contributes to the poor survival and prognosis of GBM. Defining a safe tumour volume for resection and further understanding the underlying biochemistry of glioblastoma tumour cells at the molecular level, are therefore important aspects of research that can help to improve overall patient survival. Investigation of the lipidomic changes associated with tumours is a rapidly growing field, with mass spectrometry imaging techniques widely used for molecular pathology applications. Lipidomic profiling provides downstream analysis of the proteomic and genomic changes that are also used to characterise tumours. Mass spectrometry imaging analysis by desorption electrospray ionisation mass spectrometry (DESI-MS) imaging provides an ideal toll to study investigate lipid profiles and small molecules pre-clinical model of GBM and human GBM biopsies. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging is highly specified for metal analysis and has also been used to study the metal ion distribution in the pre-clinical model of GBM, particularly that of gadolinium which was used as an MRI contrast agent alongside other endogenous metal species. The work outlined here has utilised DESI-MSI in the analysis of brain tumour samples to examine GBM at a molecular level. Overall survival in GBM has not improved for the last 15 years, so a full understanding of GBM at the molecular level is required in the hope to find new therapeutic strategies. Untargeted DESI-MS acquisition has allowed the generation of hundreds of lipid images, with subsequent multivariate statistical analysis revealing key molecular pathways implicated in GBM. Phosphatidylinositol lipid signalling molecules and overexpression of the PI3-K pathway as well as altered metabolism via beta-oxidation of fatty acids and carnitines have been observed in the pre-clinical models. This altered metabolic activity of GBM utilising fatty acid oxidation for energy production translated to human glioblastoma biopsies, where large number of acyl-carnitines were also detected. The use of histology stains other than H&E have been investigated for compatibility with DESI-MS lipidomic analysis. Cresyl violet, toluidine blue, and methylene blue staining showing compatibility with DESI-MS imaging analysis which could provide an alternative data directed stream for targeted tissue analysis.
Date of Award1 Aug 2022
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorNicholas Lockyer (Supervisor), Alan Jackson (Supervisor) & Adam McMahon (Supervisor)


  • Brain Tumour
  • Glioblastoma
  • Mass spectrometry imaging
  • Cancer

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