MALDI Imaging Mass Spectrometry of High-Grade Gliomas: A Review of Recent Progress and Future Perspective

Abstract

Glioblastoma (GBM) is the most common malignancy of the brain with a relatively short median survival and high mortality. Advanced age, high socioeconomic status, exposure to ionizing radiation, and other factors have been correlated with an increased incidence of GBM, while female sex hormones, history of allergies, and frequent use of specific drugs might exert protective effects against this disease. However, none of these explain the pathogenesis of GBM. The most recent WHO classification of CNS tumors classifies neoplasms based on their histopathological and molecular characteristics. Modern laboratory techniques, such as matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry, enable the comprehensive metabolic analysis of the tissue sample. MALDI imaging is able to characterize the spatial distribution of a wide array of biomolecules in a sample, in combination with histological features, without sacrificing the tissue integrity. In this review, we first provide an overview of GBM epidemiology, risk, and protective factors, as well as the recent WHO classification of CNS tumors. We then provide an overview of mass spectrometry workflow, with a focus on MALDI imaging, and recent advances in cancer research. Finally, we conclude the review with studies of GBM that utilized MALDI imaging and offer our perspective on future research.

Personalized Treatment of Glioblastoma: Current State and Future Perspective

“…There are many molecular targeting agents in development with encouraging results, however, as of yet these agents have not been implemented in everyday practice [ 34 ]. A novel development which might significantly improve the extent of resection is the intraoperative mass spectrometry [ 35 ]. In particular, desorption electrospray ionization (DESI) mass spectrometry could be an invaluable intraoperative tool to determine the presence of tumor cells in a studied sample, with almost real-time feedback [ 36 ].…”

“…Unfortunately, proteins in GBM are not highly tumor-specific, and generating immunity against those proteins might lead to undesired autoimmune reactions [ 108 ]. Another obstacle is a significant heterogeneity of tumor cells within GBM in the same patient [ 35 ]. Therefore, progress has been slow, but advances have still been achieved.…”

“…In conclusion, vaccine immunotherapies are often limited by targeting a single antigen, which might not be a viable strategy to treat GBM because of its high heterogeneity [ 35 ]. This problem could be solved by developing personalized GBM vaccines.…”

Untargeted Pixel-by-Pixel Imaging of Metabolite Ratio Pairs as a Novel Tool for Biomedical Discovery in Mass Spectrometry Imaging

“…Recent developments in mass spectrometry imaging (MSI) enable spatial mapping of the relative distribution and abundances of proteins, peptides, lipids, small molecule metabolites, drugs and elemental isotopes in heterogeneous tissue sections 1 with resolution at, or near, cellular 2 . Hence, MSI has become a promising tool in the era of spatial-omics [3][4][5][6][7][8][9][10][11][12][13][14][15] , especially at the single cell level 16 . Matrixassisted laser desorption and ionization (MALDI) and desorption electrospray ionization (DESI) are the dominant modes of ionization for MSI.…”