Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH‐mutated gliomas revealed by mass spectrometry imaging

Abstract

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. High infiltration rates and poor therapy responses make it the deadliest glioma. The tumor metabolism is known to differ from normal one and is influenced through various factors which can lead to longer survival. Metabolites are small molecules (< 1500 Da) that display the metabolic pathways in the tissue. To determine the metabolic alterations between tumor and peritumoral tissue in human GBMs, mass spectrometry imaging (MSI) was performed on thin sections from 25 resected tumors. In addition, the GBMs were compared with six gliomas harboring a mutation in the isocitrate dehydrogenase (IDH1) gene (IDH1). With this technique, a manifold of analytes can be easily visualized on a single tissue section. Metabolites were annotated based on their accurate mass using high resolution MSI. Differences in their mean intensities in the tumor and peritumoral areas were statistically evaluated and abundances were visualized on the tissue. Enhanced levels of the antioxidants ascorbic acid, taurine, and glutathione in tumor areas suggest protective effects on the tumor. Increased levels of purine and pyrimidine metabolism compounds in GBM areas indicate the high energy demand. In accordance with these results, enhanced abundances of lactate and glutamine were detected. Moreover, decreased abundance of N-acetylaspartate, a marker for neuronal health, was measured in tumor areas. Obtained metabolic information could potentially support and personalize therapeutic approaches, hence emphasizing the suitability of MSI for GBM research.

Lipidomic analysis and diagnosis of glioblastoma multiforme with rapid evaporative ionization mass spectrometry

“…Even though a mass of studies had proved the disorder of lipid metabolism in GBM, the essential mechanism responsible for this alteration is unclear [19, 20, 24, 27]. Some key genes in charge of lipid metabolism regulation were found to be overexpressed and the oncogenic signaling pathways had been demonstrated to be related to lipid metabolism reprogramming in GBM [28, 29].…”

Understanding the glioblastoma tumor biology to optimize photodynamic therapy: From molecular to cellular events

“…In 80% of all cases in which tumor recurrence was observed after surgery, such recurrence was found to be within 2 cm of the resected margin (Wallner et al, 1989). As it was described previously, the significant tissue heterogeneity of GBMs, as well as heterogeneity in metabolism within the tumor and in the peritumoral regions could have an impact in the efficiency of PDT (Gallaher et al, 2020;Kampa et al, 2020). These areas have been revealed by complementary techniques such as magnetic resonance…”

“…In 80% of all cases in which tumor recurrence was observed after surgery, such recurrence was found to be within 2 cm of the resected margin (Wallner et al., 1989). As it was described previously, the significant tissue heterogeneity of GBMs, as well as heterogeneity in metabolism within the tumor and in the peritumoral regions could have an impact in the efficiency of PDT (Gallaher et al, 2020; Kampa et al, 2020). These areas have been revealed by complementary techniques such as magnetic resonance imaging (MRI), where regions of contrast enhancement are observed representing the areas of greater tumor malignancy distinguishing from large necrotic areas, which tend to be located in central areas of the tumor enhancing even more the contrast (Leu et al, 2018).…”

Glutamine Imaging: A New Avenue for Glioma Management

“…MSI quantifies the spatial distribution of metabolites including glutamine by conducting mass spectrometry experiments of thin tissue slices (Fig 3). 56 MSI of human glioblastoma samples shows significant increases in glutamine, glutamate, and lactate in the tumor region compared with peritumoral and nontumoral regions. 56 Advanced MSI methods including ultra-highresolution MSI based on Fourier-transform mass spectrometry also reveal heterogeneous distributions of metabolites related to both the TCA cycle and glutamine metabolism in mouse glioblastoma tissue.…”